Search tips
Search criteria

Results 1-25 (32)

Clipboard (0)

Select a Filter Below

more »
Year of Publication
more »
1.  Allergic sensitization: screening methods 
Experimental in silico, in vitro, and rodent models for screening and predicting protein sensitizing potential are discussed, including whether there is evidence of new sensitizations and allergies since the introduction of genetically modified crops in 1996, the importance of linear versus conformational epitopes, and protein families that become allergens. Some common challenges for predicting protein sensitization are addressed: (a) exposure routes; (b) frequency and dose of exposure; (c) dose-response relationships; (d) role of digestion, food processing, and the food matrix; (e) role of infection; (f) role of the gut microbiota; (g) influence of the structure and physicochemical properties of the protein; and (h) the genetic background and physiology of consumers. The consensus view is that sensitization screening models are not yet validated to definitively predict the de novo sensitizing potential of a novel protein. However, they would be extremely useful in the discovery and research phases of understanding the mechanisms of food allergy development, and may prove fruitful to provide information regarding potential allergenicity risk assessment of future products on a case by case basis. These data and findings were presented at a 2012 international symposium in Prague organized by the Protein Allergenicity Technical Committee of the International Life Sciences Institute’s Health and Environmental Sciences Institute.
PMCID: PMC3990213  PMID: 24739743
3.  Multiple Chronic Conditions Among US Adults: A 2012 Update 
The objective of this research was to update earlier estimates of prevalence rates of single chronic conditions and multiple (>2) chronic conditions (MCC) among the noninstitutionalized, civilian US adult population. Data from the 2012 National Health Interview Survey (NHIS) were used to generate estimates of MCC for US adults and by select demographic characteristics. Approximately half (117 million) of US adults have at least one of the 10 chronic conditions examined (ie, hypertension, coronary heart disease, stroke, diabetes, cancer, arthritis, hepatitis, weak or failing kidneys, current asthma, or chronic obstructive pulmonary disease [COPD]). Furthermore, 1 in 4 adults has MCC.
PMCID: PMC3992293  PMID: 24742395
4.  Multiple Chronic Conditions Among Medicare Beneficiaries: State-level Variations in Prevalence, Utilization, and Cost, 2011 
Medicare & Medicaid Research Review  2013;3(3):mmrr.003.03.b02.
Individuals with multiple (>2) chronic conditions (MCC) present many challenges to the health care system, such as effective coordination of care and cost containment. To assist health policy makers and to fill research gaps on MCC, we describe state-level variation of MCC among Medicare beneficiaries, with a focus on those with six or more conditions.
Using Centers for Medicare & Medicaid Services administrative data for 2011, we characterized a beneficiary as having MCC by counting the number of conditions from a set of fifteen conditions, which were identified using diagnosis codes on the claims. The study population included fee-for-service beneficiaries residing in the 50 U.S. states and Washington, DC
Among beneficiaries with six or more chronic conditions, prevalence rates were lowest in Alaska and Wyoming (7%) and highest in Florida and New Jersey (18%); readmission rates were lowest in Utah (19%) and highest in Washington, DC (31%); the number of emergency department visits per beneficiary were lowest in New York and Florida (1.6) and highest in Washington, DC (2.7); and Medicare spending per beneficiary was lowest in Hawaii ($24,086) and highest in Maryland, Washington, DC, and Louisiana (over $37,000).
These findings expand upon prior research on MCC among Medicare beneficiaries at the national level and demonstrate considerable state-level variation in the prevalence, health care utilization, and Medicare spending for beneficiaries with MCC. State-level data on MCC is important for decision making aimed at improved program planning, financing, and delivery of care for individuals with MCC.
PMCID: PMC3983735  PMID: 24753976
Administrative Data Uses; Chronic Disease; Geographic; Spatial Factors; Small area variations; Medicare
6.  Defining and Measuring Chronic Conditions: Imperatives for Research, Policy, Program, and Practice 
Current trends in US population growth, age distribution, and disease dynamics foretell rises in the prevalence of chronic diseases and other chronic conditions. These trends include the rapidly growing population of older adults, the increasing life expectancy associated with advances in public health and clinical medicine, the persistently high prevalence of some risk factors, and the emerging high prevalence of multiple chronic conditions. Although preventing and mitigating the effect of chronic conditions requires sufficient measurement capacities, such measurement has been constrained by lack of consistency in definitions and diagnostic classification schemes and by heterogeneity in data systems and methods of data collection. We outline a conceptual model for improving understanding of and standardizing approaches to defining, identifying, and using information about chronic conditions in the United States. We illustrate this model’s operation by applying a standard classification scheme for chronic conditions to 5 national-level data systems.
PMCID: PMC3652713  PMID: 23618546
7.  Co-Occurrence of Leading Lifestyle-Related Chronic Conditions Among Adults in the United States, 2002-2009 
Public health and clinical strategies for meeting the emerging challenges of multiple chronic conditions must address the high prevalence of lifestyle-related causes. Our objective was to assess prevalence and trends in the chronic conditions that are leading causes of disease and death among adults in the United States that are amenable to preventive lifestyle interventions.
We used self-reported data from 196,240 adults aged 25 years or older who participated in the National Health Interview Surveys from 2002 to 2009. We included data on cardiovascular disease (coronary heart disease, angina pectoris, heart attack, and stroke), cancer, chronic obstructive pulmonary disease (emphysema and chronic bronchitis), diabetes, and arthritis.
In 2002, an unadjusted 63.6% of participants did not have any of the 5 chronic conditions we assessed; 23.9% had 1, 9.0% had 2, 2.9% had 3, and 0.7% had 4 or 5. By 2009, the distribution of co-occurrence of the 5 chronic conditions had shifted subtly but significantly. From 2002 to 2009, the age-adjusted percentage with 2 or more chronic conditions increased from 12.7% to 14.7% (P < .001), and the number of adults with 2 or more conditions increased from approximately 23.4 million to 30.9 million.
The prevalence of having 1 or more or 2 or more of the leading lifestyle-related chronic conditions increased steadily from 2002 to 2009. If these increases continue, particularly among younger adults, managing patients with multiple chronic conditions in the aging population will continue to challenge public health and clinical practice.
PMCID: PMC3652715  PMID: 23618540
8.  Clinical Use of Probiotics in Pediatric Allergy (cuppa): A World Allergy Organization Position Paper 
Probiotic administration has been proposed for the prevention and treatment of specific allergic manifestations such as eczema, rhinitis, gastrointestinal allergy, food allergy, and asthma. However, published statements and scientific opinions disagree about the clinical usefulness.
A World Allergy Organization Special Committee on Food Allergy and Nutrition review of the evidence regarding the use of probiotics for the prevention and treatment of allergy.
A qualitative and narrative review of the literature on probiotic treatment of allergic disease was carried out to address the diversity and variable quality of relevant studies. This variability precluded systematization, and an expert panel group discussion method was used to evaluate the literature. In the absence of systematic reviews of treatment, meta-analyses of prevention studies were used to provide data in support of probiotic applications.
Despite the plethora of literature, probiotic research is still in its infancy. There is a need for basic microbiology research on the resident human microbiota. Mechanistic studies from biology, immunology, and genetics are needed before we can claim to harness the potential of immune modulatory effects of microbiota. Meanwhile, clinicians must take a step back and try to link disease state with alterations of the microbiota through well-controlled long-term studies to identify clinical indications.
Probiotics do not have an established role in the prevention or treatment of allergy. No single probiotic supplement or class of supplements has been demonstrated to efficiently influence the course of any allergic manifestation or long-term disease or to be sufficient to do so. Further epidemiologic, immunologic, microbiologic, genetic, and clinical studies are necessary to determine whether probiotic supplements will be useful in preventing allergy. Until then, supplementation with probiotics remains empirical in allergy medicine. In the future, basic research should focus on homoeostatic studies, and clinical research should focus on preventive medicine applications, not only in allergy. Collaborations between allergo-immunologists and microbiologists in basic research and a multidisciplinary approach in clinical research are likely to be the most fruitful.
PMCID: PMC3651185  PMID: 23282383
probiotics; prevention of allergy; pediatric allergy
9.  Implementation and Impact of a Translational Research Training Program in Pulmonary and Critical Care Medicine* 
Chest  2008;135(3):688-694.
The translation of basic research advances to the clinical arena has been slow and inefficient. With the goal of improving interactions and collaboration between basic science and clinical investigators, we instituted a Translational Research Training Program (TRTP) in acute lung injury to complement our basic science and clinical research training programs in pulmonary and critical care medicine.
We developed a TRTP in which trainees select a primary research discipline for rigorous development of skills in either basic science research or clinical research. This primary foundation is complemented by cross-training in the other discipline through a specifically designed program of study. To measure the impact of the program, we analyzed publication rates, coauthorship to reflect collaboration between research disciplines, and publication of papers with a translational focus by members of our division before and after the institution of the TRTP.
We describe our new training program, including modifications to our preexisting program and development of new components. We found significant increases in multidisciplinary authorship and translational articles following institution of TRTP.
An explicit TRTP appears to increase collaboration between basic and clinical investigators. Our goal is to share our experiences and provide a template for other pulmonary and critical care programs interested in developing similar curricula. We speculate that this training will improve the translation of basic research findings into clinical advances, thus increasing the probability that successful treatments will be developed for patients with lung diseases.
PMCID: PMC3468153  PMID: 19017887
curriculum; education; graduate; medical; pulmonary and critical care; specialty; training
10.  Managing Multiple Chronic Conditions: A Strategic Framework for Improving Health Outcomes and Quality of Life 
Public Health Reports  2011;126(4):460-471.
The escalating problem of multiple chronic conditions (MCC) among Americans is now a major public health and medical challenge, associated with suboptimal health outcomes and rising health-care expenses. Despite this problem's growth, the delivery of health services has continued to employ outmoded “siloed” approaches that focus on individual chronic diseases. We describe an action-oriented framework—developed by the U.S. Department of Health and Human Services with additional input provided by stakeholder organizations—that outlines national strategies for maximizing care coordination and for improving health and quality of life for individuals with MCC. We note how the framework's potential can be optimized through some of the provisions of the new Patient Protection and Affordable Care Act, and through public-private partnerships.
PMCID: PMC3115206  PMID: 21800741
11.  Breast Milk α-Defensins Are Associated with HIV Type 1 RNA and CC Chemokines in Breast Milk But Not Vertical HIV Type 1 Transmission 
α-Defensins are proteins exhibiting in vitro anti-HIV-1 activity that may protect against mother-to-child transmission of HIV-1 via breast milk. Correlates of α-defensins in breast milk and transmission risk were determined in a cohort of HIV-1-infected pregnant women in Nairobi followed for 12 months postpartum with their infants. Maternal blood was collected antenatally and at delivery for HIV-1 viral load and infant HIV-1 infection status was determined <48 h after birth and at months 1, 3, 6, 9, and 12. Breast milk specimens collected at month 1 were assayed for α-defensins, HIV-1 RNA, subclinical mastitis, and CC and CXC chemokines. We detected α-defensins in breast milk specimens from 108 (42%) of 260 HIV-1-infected women. Women with detectable α-defensins (≥50 pg/ml) had a median concentration of 320 pg/ml and significantly higher mean breast milk HIV-1 RNA levels than women with undetectable α-defensins (2.9 log10 copies/ml versus 2.5 log10 copies/ml, p = 0.003). Increased α-defensins concentrations in breast milk were also associated with subclinical mastitis (Na+/K+ ratio > 1) and increased breast milk chemokine levels. Overall, 40 (15%) infants were HIV-1 uninfected at birth and subsequently acquired HIV-1. There was no significant association between month 1 α-defensins and risk of HIV-1 transmission. In conclusion, α-defensins were associated with breast milk HIV-1 viral load, chemokine levels, and subclinical mastitis, all of which may alter risk of infant HIV-1 acquisition. Despite these associations there was no significant relationship between breast milk α-defensins and mother-to-child transmission, suggesting a complex interplay between breast milk HIV-1, inflammation, and antiinfective factors.
PMCID: PMC3382116  PMID: 17331027
12.  15 A Bioinformatic Approach to Allergen Nomenclature Applied to Allergens From the Non-Biting Midge Chironomus thummi thummi 
The World Allergy Organization Journal  2012;5(Suppl 2):S22-S23.
Representatives of the family Chironomidae (non-biting midges; order Diptera) are found worldwide. Freeze-dried chironomid larvae, predominantly of the species Chironomus thummi thummi are frequently used as fish food and are an allergen source for fish keepers and persons employed in the manufacture of fish food. At present, 9 allergens of C. thummi thummi have been assigned an official designation by the WHO/IUIS allergen nomenclature sub-committee: Chi t 1 to 9. All of them are hemoglobins with molecular weights of 16 kDa. IgE binding and cross-reactivity was clearly demonstrated for all these proteins. However, the assignment of 9 distinct allergen numbers to members of the same protein family is quite unusual.
Currently, the IUIS allergen database contains 12 allergen and isoallergen sequences from C. thummi thummi. The Uniprot database has demerged entry P02225, listed in the database for Chi t 7, into 7 entries, 5 from C. thummi thummi and 2 from C. thummi piger that are identical to 2 of the sequences from C. thummi thummi. Consequently, the 16 unique amino acid sequences of the mature C. thummi allergens were aligned using ClustalX2, a neighbor-joining tree was generated from the alignment and a percent sequence identity matrix was built to evaluate appropriate nomenclature.
Pairwise sequence alignments showed that sequences belonging to allergens Chi t 5, 6, 7 and 8 possess sequence identities to Chi t 3 of between 51 and 63%. Chi t 1, 2, 4, and 9 diverge to a greater extent from Chi t 3 (<50% identical) and from each other. Phylogenetic tree analysis suggests the clustering of Chi t 3, 6, 7, and 8, while Chi t 1, 2, 4, 5, and 9 form separate clades.
Based on these analyses, the IUIS Allergen Nomenclature Sub-Committee renames Chi t 5, 6, 7 and 8 isoallergens of Chi t 3, even though their sequence identities to Chi t 3 are below the 67% threshold previously defined for isoallergens. The remaining hemoglobins, previously designated Chi t 1, 2, 4 and 9 will retain their previous names.
PMCID: PMC3513063
14.  Suggested Improvements for the Allergenicity Assessment of Genetically Modified Plants Used in Foods 
Genetically modified (GM) plants are increasingly used for food production and industrial applications. As the global population has surpassed 7 billion and per capita consumption rises, food production is challenged by loss of arable land, changing weather patterns, and evolving plant pests and disease. Previous gains in quantity and quality relied on natural or artificial breeding, random mutagenesis, increased pesticide and fertilizer use, and improved farming techniques, all without a formal safety evaluation. However, the direct introduction of novel genes raised questions regarding safety that are being addressed by an evaluation process that considers potential increases in the allergenicity, toxicity, and nutrient availability of foods derived from the GM plants. Opinions vary regarding the adequacy of the assessment, but there is no documented proof of an adverse effect resulting from foods produced from GM plants. This review and opinion discusses current practices and new regulatory demands related to food safety.
PMCID: PMC3130127  PMID: 21487714
Allergenicity; Food safety; Genetically modified; IgE; Risk assessment; Improvement; Plants
15.  Towards Defining Molecular Determinants Recognized by Adaptive Immunity in Allergic Disease: An Inventory of the Available Data 
Journal of Allergy  2011;2010:628026.
Adaptive immune responses associated with allergic reactions recognize antigens from a broad spectrum of plants and animals. Herein a meta-analysis was performed on allergy-related data from the immune epitope database (IEDB) to provide a current inventory and highlight knowledge gaps and areas for future work. The analysis identified over 4,500 allergy-related epitopes derived from 270 different allergens. Overall, the distribution of the data followed expectations based on the nature of allergic responses. Namely, the majority of epitopes were defined for B cells/antibodies and IgE-mediated reactivity, and relatively fewer T-cell epitopes, mostly CD4+/class II. Interestingly, the majority of food allergen epitopes were B-cells epitopes whereas a fairly even number of B- and T-cell epitopes were defined for airborne allergens. In addition, epitopes from nonhumans hosts were mostly T-cell epitopes. Overall, coverage of known allergens is sparse with data available for only ~17% of all allergens listed by the IUIS database. Thus, further research would be required to provide a more balanced representation across different allergen categories. Furthermore, inclusion of nonpeptidic epitopes in the IEDB also allows for inventory and analysis of immunological data associated with drug and contact allergen epitopes. Finally, our analysis also underscores that only a handful of epitopes have thus far been investigated for their immunotherapeutic potential.
PMCID: PMC3042621  PMID: 21403821
16.  The biological activity of FasL in human and mouse lungs is determined by the structure of its stalk region 
The Journal of Clinical Investigation  2011;121(3):1174-1190.
Acute lung injury (ALI) is a life-threatening condition in critically ill patients. Injury to the alveolar epithelium is a critical event in ALI, and accumulating evidence suggests that it is linked to proapoptotic Fas/FasL signals. Active soluble FasL (sFasL) is detectable in the bronchoalveolar lavage (BAL) fluid of patients with ALI, but the mechanisms controlling its bioactivity are unclear. We therefore investigated how the structure of sFasL influences cellular activation in human and mouse lungs and the role of oxidants and proteases in modifying sFasL activity. The sFasL in BAL fluid from patients with ALI was bioactive and present in high molecular weight multimers and aggregates. Oxidants generated from neutrophil myeloperoxidase in BAL fluid promoted aggregation of sFasL in vitro and in vivo. Oxidation increased the biological activity of sFasL at low concentrations but degraded sFasL at high concentrations. The amino-terminal extracellular stalk region of human sFasL was required to induce lung injury in mice, and proteolytic cleavage of the stalk region by MMP-7 reduced the bioactivity of sFasL in human cells in vitro. The sFasL recovered from the lungs of patients with ALI contained both oxidized methionine residues and the stalk region. These data provide what we believe to be new insights into the structural determinants of sFasL bioactivity in the lungs of patients with ALI.
PMCID: PMC3049393  PMID: 21285513
17.  An activity-induced microRNA controls dendritic spine formation by regulating Rac1-PAK signaling 
Activity-regulated gene expression is believed to play a key role in the development and refinement of neuronal circuitry. Nevertheless, the transcriptional networks that regulate synaptic plasticity remain largely uncharacterized. We show here that the CREB- and activity-regulated microRNA, miR132, is induced during periods of active synaptogenesis. Moreover, miR132 is necessary and sufficient for hippocampal spine formation. Expression of the miR132 target, p250GAP, is inversely correlated with miR132 levels and spinogenesis. Furthermore, knockdown of p250GAP increases spine formation while introduction of a p250GAP mutant unresponsive to miR132 attenuates this activity. Inhibition of miR132 decreases both mEPSC frequency and the number of GluR1-positive spines, while knockdown of p250GAP has the opposite effect. Additionally, we show that the miR132/p250GAP circuit regulates Rac1 activity and spine formation by modulating synapse-specific Kalirin7-Rac1 signaling. These data suggest that neuronal activity regulates spine formation, in part, by increasing miR132 transcription, which in turn activates a Rac1-Pak actin remodeling pathway.
PMCID: PMC2818337  PMID: 19850129
18.  A Genome-Wide Screen for β-Catenin Binding Sites Identifies a Downstream Enhancer Element That Controls c-Myc Gene Expression ▿  
Molecular and Cellular Biology  2008;28(24):7368-7379.
Mutations in components of the Wnt signaling pathway initiate colorectal carcinogenesis by deregulating the β-catenin transcriptional coactivator. β-Catenin activation of one target in particular, the c-Myc proto-oncogene, is required for colon cancer pathogenesis. β-Catenin is known to regulate c-Myc expression via sequences upstream of the transcription start site. Here, we report that a more robust β-catenin binding region localizes 1.4 kb downstream from the c-Myc transcriptional stop site. This site was discovered using a genome-wide method for identifying transcription factor binding sites termed serial analysis of chromatin occupancy. Chromatin immunoprecipitation-scanning assays demonstrate that the 5′ enhancer and the 3′ binding element are the only β-catenin and TCF4 binding regions across the c-Myc locus. When placed downstream of a simian virus 40-driven promoter-luciferase construct, the 3′ element activated luciferase transcription when introduced into HCT116 cells. c-Myc transcription is negligible in quiescent HCT116 cells but is induced when cells reenter the cell cycle after the addition of mitogens. Using these cells, we found that β-catenin and TCF4 occupancy at the 3′ enhancer precede occupancy at the 5′ enhancer. Association of c-Jun, β-catenin, and TCF4 specifically with the downstream enhancer underlies mitogen stimulation of c-Myc transcription. Our findings indicate that a downstream enhancer element provides the principal regulation of c-Myc expression.
PMCID: PMC2593444  PMID: 18852287
19.  Delinquent Mortgages, Neglected Swimming Pools, and West Nile Virus, California 
Emerging Infectious Diseases  2009;14(3):1747-9.
PMCID: PMC2681132  PMID: 19239785
West Nile virus; mosquitoes; surveillance; mortgages; swimming pools; California; letter
20.  Bioviolence: Preventing Biological Terror and Crime 
Emerging Infectious Diseases  2008;14(2):355-356.
PMCID: PMC2600217
21.  Distribution of Menin-Occupied Regions in Chromatin Specifies a Broad Role of Menin in Transcriptional Regulation1* 
Neoplasia (New York, N.Y.)  2007;9(2):101-107.
Menin is the protein product of the MEN1 tumor-suppressor gene; one allele of MEN1 is inactivated in the germ line of patients with “multiple endocrine neoplasia type 1” (MEN1) cancer syndrome. Menin interacts with several proteins involved in transcriptional regulation. RNA expression analyses have identified several menin-regulated genes that could represent proximal or distal interaction sites for menin. This report presents a substantial and unbiased sampling of menin-occupied chromatin regions using Serial Analysis of Chromatin Occupancy; this method combines chromatin immuno-precipitation with Serial Analysis of Gene Expression. Hundreds of menin-occupied genomic sites were identified in promoter regions (32% of menin-occupied loci), near the 3′ end of genes (14%), or inside genes (21%), extending other data about menin recruitments to many sites of transcriptional activity. A large number of menin-occupied sites (33%) were located outside known gene regions. Additional annotation of the human genome could help in identifying genes at these loci, or these might be gene-free regions of the genome where menin occupancy could play some structural or regulatory role. Menin occupancy at many intragenic positions distant from the core promoter reveals an unexpected type of menin target region at many loci in the genome. These unbiased data also suggest that menin could play a broad role in transcriptional regulation.
PMCID: PMC1813935  PMID: 17356705
MEN1; multiple endocrine neoplasia; SACO; chromatin immunoprecipitation; ChIP
23.  Law as a Tool for Preventing Chronic Diseases: Expanding the Spectrum of Effective Public Health Strategies 
Preventing Chronic Disease  2003;1(1):A13.
Law, which is a fundamental element of effective public health policy and practice, played a crucial role in many of public health's greatest achievements of the 20th century. Still, conceptual legal frameworks for the systematic application of law to chronic disease prevention and control have not been fully recognized and used to address public health needs. Development and implementation of legal frameworks could broaden the range of effective public health strategies and provide valuable tools for the public health workforce, especially for state and local health department program managers and state and national policy makers. In an effort to expand the range of effective public health interventions, the Centers for Disease Control and Prevention will work with its partners to explore the development of systematic legal frameworks as a tool for preventing chronic diseases and addressing the growing epidemic of obesity, heart disease, stroke, and other chronic diseases and their risk factors.
PMCID: PMC544536  PMID: 15634375
24.  The Acetyltransferase Activity of CBP Is Required for wingless Activation and H4 Acetylation in Drosophila melanogaster 
Molecular and Cellular Biology  2002;22(11):3832-3841.
CBP is a critical coactivator of transcription, but little is understood about the importance of its intrinsic acetyltransferase (AT) activity in gene activation in vivo. We show that the intrinsic AT function of CBP in Drosophila melanogaster (dCBP) is necessary to maintain a dCBP overexpression phenotype in the eye, for the in vivo activation of a specific target gene, wingless, and for the global acetylation of histone H4. These findings indicate that a point mutation which alters the intrinsic AT activity of CBP (only one of many CBP functions) has profound effects on CBP-induced gene activation in a physiologically intact transcription system. Furthermore, the effects of CBP AT activity are not limited to a few specific promoters, but rather CBT AT activity may play a role in regulating global histone acetylation throughout the developing organism.
PMCID: PMC133831  PMID: 11997517
25.  Acetylation of Nuclear Hormone Receptor-Interacting Protein RIP140 Regulates Binding of the Transcriptional Corepressor CtBP 
Molecular and Cellular Biology  2001;21(18):6181-6188.
CtBP (carboxyl-terminal binding protein) participates in regulating cellular development and differentiation by associating with a diverse array of transcriptional repressors. Most of these interactions occur through a consensus CtBP-binding motif, PXDLS, in the repressor proteins. We previously showed that the CtBP-binding motif in E1A is flanked by a Lys residue and suggested that acetylation of this residue by the p300/CBP-associated factor P/CAF disrupts the CtBP interaction. In this study, we show that the interaction between CtBP and the nuclear hormone receptor corepressor RIP140 is regulated similarly, in this case by p300/CBP itself. CtBP was shown to interact with RIP140 in vitro and in vivo through a sequence, PIDLSCK, in the amino-terminal third of the RIP140 protein. Acetylation of the Lys residue in this motif, demonstrated in vivo by using an acetylated RIP140-specific antibody, dramatically reduced CtBP binding. Mutation of the Lys residue to Gln resulted in a decrease in CtBP binding in vivo and a loss of transcriptional repression. We suggest that p300/CBP-mediated acetylation disrupts the RIP140-CtBP complex and derepresses nuclear hormone receptor-regulated genes. Disruption of repressor-CtBP interactions by acetylation may be a general mode of gene activation.
PMCID: PMC87335  PMID: 11509661

Results 1-25 (32)