PMCC PMCC

Search tips
Search criteria

Advanced
Results 1-25 (113)
 

Clipboard (0)
None

Select a Filter Below

Journals
Year of Publication
1.  S100A8/A9 induces autophagy and apoptosis via ROS-mediated cross-talk between mitochondria and lysosomes that involves BNIP3 
Cell research  2009;20(3):314-331.
The complex formed by two members of the S100 calcium-binding protein family, S100A8/A9, exerts apoptosis-inducing activity in various cells of different origins. Here, we present evidence that the underlying molecular mechanisms involve both programmed cell death I (PCD I, apoptosis) and PCD II (autophagy)-like death. Treatment of cells with S100A8/A9 caused the increase of Beclin-1 expression as well as Atg12-Atg5 formation. S100A8/A9-induced cell death was partially inhibited by the specific PI3-kinase class III inhibitor, 3-methyladenine (3-MA), and by the vacuole H+-ATPase inhibitor, bafilomycin-A1 (Baf-A1). S100A8/A9 provoked the translocation of BNIP3, a BH3 only pro-apoptotic Bcl2 family member, to mitochondria. Consistent with this finding, ΔTM-BNIP3 overexpression partially inhibited S100A8/A9-induced cell death, decreased reactive oxygen species (ROS) generation, and partially protected against the decrease in mitochondrial transmembrane potential in S100A8/A9-treated cells. In addition, either ΔTM-BNIP3 overexpression or N-acetyl-L-cysteine co-treatment decreased lysosomal activation in cells treated with S100A8/A9. Our data indicate that S100A8/A9-promoted cell death occurs through the cross-talk of mitochondria and lysosomes via ROS and the process involves BNIP3.
doi:10.1038/cr.2009.129
PMCID: PMC4161879  PMID: 19935772
S100A8/A9; Calprotectin; lysosomal activation; mitochondrial membrane potential; BNIP3; Beclin-1
2.  Metamorphosis of the malaria parasite in the liver is associated with organelle clearance 
Cell research  2010;20(9):1043-1059.
Malaria parasites encounter diverse conditions as they cycle between their vertebrate host and mosquito vector. Within these distinct environments, the parasite undergoes drastic transformations, changing both its morphology and metabolism. Plasmodium species that infect mammals must first take up residence in the liver before initiating red blood cell infection. Following penetration into hepatocytes, the parasite converts from an invasion-competent, motile, elongated sporozoite to a metabolically active, round trophozoite. Relatively little is known about the cellular events involved in sporozoite metamorphosis. Our data uncover the early cellular events associated with these transformations. We illustrate that the beginning of metamorphosis is marked by the disruption of the membrane cytoskeleton beneath the plasma membrane, which results in a protruding area around the nucleus. As this bulbous region expands, the two distal ends of the sporozoite gradually retract and disappear, leading to cell sphericalization. This shape change is associated with major interior renovations and clearance of superfluous organelles, e.g. micronemes involved in invasion. The membrane cytoskeleton is reorganized into dense lamellar arrays within the cytoplasm and is partially expulsed by converting parasites. Simultaneously, micronemes are compartmentalized into large exocytic vesicles and are then discharged into the environment. At the completion of metamorphosis, the parasites only retain organelles necessary for replication. These observations lay the groundwork for further investigations on the developmental pathways implicated in the metamorphosis of the malaria parasite.
doi:10.1038/cr.2010.88
PMCID: PMC4137911  PMID: 20567259
Malaria; hepatic stage; differentiation; membrane cytoskeleton; micronemes; exocytosis
3.  AOF1 is a histone H3K4 demethylase possessing demethylase activity-independent repression function 
Cell research  2010;20(3):276-287.
LSD1 (KDM1 under the new nomenclature) was the first identified lysine-specific histone demethylase belonging to the flavin-dependent amine oxidase family. Here, we report that AOF1 (KDM1B under the new nomenclature), a mammalian protein related to LSD1, also possesses histone demethylase activity with specificity for H3K4me1 and H3K4me2. Like LSD1, the highly conserved SWIRM domain is required for its enzymatic activity. However, AOF1 differs from LSD1 in several aspects. First, AOF1 does not appear to form stable protein complexes containing histone deacetylases. Second, AOF1 is found to localize to chromosomes during the mitotic phase of the cell cycle, whereas LSD1 does not. Third, AOF1 represses transcription when tethered to DNA and this repression activity is independent of its demethylase activity. Structural and functional analyses identified its unique N-terminal Zf-CW domain as essential for the demethylase activity-independent repression function. Collectively, our study identifies AOF1 as the second histone demethylase in the family of flavin-dependent amine oxidases and reveals a demethylase-independent repression function of AOF1.
doi:10.1038/cr.2010.12
PMCID: PMC4106039  PMID: 20101264
AOF1; histone H3K4 demethylase; chromatin; repression; Zf-CW
4.  PPARs: Diverse Regulators in Energy Metabolism and Metabolic Diseases 
Cell research  2010;20(2):124-137.
The nuclear receptor PPARs are fundamentally important for energy homeostasis. Through their distinct yet overlapping functions and tissue distribution, the there PPARs regulate many aspects of energy metabolism at the transcriptional level. Functional impairment or dysregulation of these receptors leads to a variety of metabolic diseases, while their ligands offer many metabolic benefits. Studies of these receptors have advanced our knowledge of the transcriptional basis of energy metabolism and helped us understand the pathogenic mechanisms of metabolic syndrome.
doi:10.1038/cr.2010.13
PMCID: PMC4084607  PMID: 20101262
PPAR; transcriptional regulation; energy metabolism; metabolic diseases; fatty acid metabolism; obesity; insulin resistance
5.  Paneth cells and inflammation dance together in Crohn’s disease 
Cell research  2008;18(12):1160-1162.
doi:10.1038/cr.2008.312
PMCID: PMC3990404  PMID: 19043437
6.  Embracing the Complexity of Pre-mRNA Splicing 
Cell research  2010;20(8):866-868.
doi:10.1038/cr.2010.98
PMCID: PMC3912182  PMID: 20603640
alternative pre-mRNA splicing; exon; intron; computation
7.  Bmi1 poliSHHes reprogramming 
Cell research  2011;21(9):10.1038/cr.2011.126.
doi:10.1038/cr.2011.126
PMCID: PMC3193464
8.  Evidence for a critical role of gene occlusion in cell fate restriction 
Cell Research  2011;22(5):848-858.
The progressive restriction of cell fate during lineage differentiation is a poorly understood phenomenon despite its ubiquity in multicellular organisms. We recently used a cell fusion assay to define a mode of epigenetic silencing that we termed “occlusion”, wherein affected genes are silenced by cis-acting chromatin mechanisms irrespective of whether trans-acting transcriptional activators are present. We hypothesized that occlusion of lineage-inappropriate genes could contribute to cell fate restriction. Here, we test this hypothesis by introducing bacterial artificial chromosomes (BACs), which are devoid of chromatin modifications necessary for occlusion, into mouse fibroblasts. We found that BAC transgenes corresponding to occluded endogenous genes are expressed in most cases, whereas BAC transgenes corresponding to silent but non-occluded endogenous genes are not expressed. This indicates that the cellular milieu in trans supports the expression of most occluded genes in fibroblasts, and that the silent state of these genes is solely the consequence of occlusion in cis. For the BAC corresponding to the occluded myogenic master regulator Myf5, expression of the Myf5 transgene on the BAC triggered fibroblasts to acquire a muscle-like phenotype. These results provide compelling evidence for a critical role of gene occlusion in cell fate restriction.
doi:10.1038/cr.2011.190
PMCID: PMC3297702  PMID: 22124232
cell fate restriction; occlusion; bacterial artificial chromosome
9.  [No title available] 
PMCID: PMC3639319  PMID: 18166979
10.  Revealing a steroid receptor ligand as a unique PPARγ agonist 
Cell Research  2011;22(4):746-756.
Peroxisome proliferator-activated receptor gamma (PPARγ) regulates metabolic homeostasis and is a molecular target for anti-diabetic drugs. We report here the identification of a steroid receptor ligand, RU-486, as an unexpected PPARγ agonist, thereby uncovering a novel signaling route for this steroid drug. Similar to rosiglitazone, RU-486 modulates the expression of key PPARγ target genes and promotes adipocyte differentiation, but with a lower adipogenic activity. Structural and functional studies of receptor-ligand interactions reveal the molecular basis for a unique binding mode for RU-486 in the PPARγ ligand-binding pocket with distinctive properties and epitopes, providing the molecular mechanisms for the discrimination of RU-486 from thiazolidinediones (TZDs) drugs. Our findings together indicate that steroid compounds may represent an alternative approach for designing non-TZD PPARγ ligands in the treatment of insulin resistance.
doi:10.1038/cr.2011.162
PMCID: PMC3257359  PMID: 21986665
PPARγ; nuclear receptor; diabetes; crystal structure; steroid compound
11.  Signaling cross-talk between TGF-β/BMP and other pathways 
Cell research  2009;19(1):71-88.
Transforming growth factor-beta (TGF-β)/bone morphogenic protein (BMP) signaling is involved in the vast majority of cellular processes and is fundamentally important during the entire life of all metazoans. Deregulation of TGF-β/BMP activity almost invariably leads to developmental defects and/or diseases, including cancer. The proper functioning of the TGF-β/BMP pathway depends on its constitutive and extensive communication with other signaling pathways, leading to synergistic or antagonistic effects and eventually desirable biological outcomes. The nature of such signaling cross-talk is overwhelmingly complex and highly context-dependent. Here we review the different modes of cross-talk between TGF-β/BMP and the signaling pathways of Mitogen-activated protein kinase, phosphatidylinositol-3 kinase/Akt, Wnt, Hedgehog, Notch, and the interleukin/interferon-gamma/tumor necrosis factor-alpha cytokines, with an emphasis on the underlying molecular mechanisms.
doi:10.1038/cr.2008.302
PMCID: PMC3606489  PMID: 19002158
TGF-β; Smad; cross-talk; signaling pathway
12.  K-rasG12V transformation leads to mitochondrial dysfunction and a metabolic switch from oxidative phosphorylation to glycolysis 
Cell Research  2011;22(2):399-412.
Increased aerobic glycolysis and oxidative stress are important features of cancer cell metabolism, but the underlying biochemical and molecular mechanisms remain elusive. Using a tetracycline inducible model, we show that activation of K-rasG12V causes mitochondrial dysfunction, leading to decreased respiration, elevated glycolysis, and increased generation of reactive oxygen species. The K-RAS protein is associated with mitochondria, and induces a rapid suppression of respiratory chain complex-I and a decrease in mitochondrial transmembrane potential by affecting the cyclosporin-sensitive permeability transition pore. Furthermore, pre-induction of K-rasG12V expression in vitro to allow metabolic adaptation to high glycolytic metabolism enhances the ability of the transformed cells to form tumor in vivo. Our study suggests that induction of mitochondrial dysfunction is an important mechanism by which K-rasG12V causes metabolic changes and ROS stress in cancer cells, and promotes tumor development.
doi:10.1038/cr.2011.145
PMCID: PMC3257361  PMID: 21876558
K-ras; mitochondrial dysfunction; glycolysis
13.  K-rasG12V transformation leads to mitochondrial dysfunction and a metabolic switch from oxidative phosphorylation to glycolysis 
Cell Research  2011;22(2):399-412.
Increased aerobic glycolysis and oxidative stress are important features of cancer cell metabolism, but the underlying biochemical and molecular mechanisms remain elusive. Using a tetracycline inducible model, we show that activation of K-rasG12V causes mitochondrial dysfunction, leading to decreased respiration, elevated glycolysis, and increased generation of reactive oxygen species. The K-RAS protein is associated with mitochondria, and induces a rapid suppression of respiratory chain complex-I and a decrease in mitochondrial transmembrane potential by affecting the cyclosporin-sensitive permeability transition pore. Furthermore, pre-induction of K-rasG12V expression in vitro to allow metabolic adaptation to high glycolytic metabolism enhances the ability of the transformed cells to form tumor in vivo. Our study suggests that induction of mitochondrial dysfunction is an important mechanism by which K-rasG12V causes metabolic changes and ROS stress in cancer cells, and promotes tumor development.
doi:10.1038/cr.2011.145
PMCID: PMC3257361  PMID: 21876558
K-ras; mitochondrial dysfunction; glycolysis
14.  Oct4 links multiple epigenetic pathways to the pluripotency network 
Cell Research  2011;22(1):155-167.
Oct4 is a well-known transcription factor that plays fundamental roles in stem cell self-renewal, pluripotency, and somatic cell reprogramming. However, limited information is available on Oct4-associated protein complexes and their intrinsic protein-protein interactions that dictate Oct4's critical regulatory activities. Here we employed an improved affinity purification approach combined with mass spectrometry to purify Oct4 protein complexes in mouse embryonic stem cells (mESCs), and discovered many novel Oct4 partners important for self-renewal and pluripotency of mESCs. Notably, we found that Oct4 is associated with multiple chromatin-modifying complexes with documented as well as newly proved functional significance in stem cell maintenance and somatic cell reprogramming. Our study establishes a solid biochemical basis for genetic and epigenetic regulation of stem cell pluripotency and provides a framework for exploring alternative factor-based reprogramming strategies.
doi:10.1038/cr.2011.179
PMCID: PMC3252465  PMID: 22083510
Oct4; ESCs; pluripotency; self-renewal; epigenetic regulation
15.  The metabolome of induced pluripotent stem cells reveals metabolic changes occurring in somatic cell reprogramming 
Cell Research  2011;22(1):168-177.
Metabolism is vital to every aspect of cell function, yet the metabolome of induced pluripotent stem cells (iPSCs) remains largely unexplored. Here we report, using an untargeted metabolomics approach, that human iPSCs share a pluripotent metabolomic signature with embryonic stem cells (ESCs) that is distinct from their parental cells, and that is characterized by changes in metabolites involved in cellular respiration. Examination of cellular bioenergetics corroborated with our metabolomic analysis, and demonstrated that somatic cells convert from an oxidative state to a glycolytic state in pluripotency. Interestingly, the bioenergetics of various somatic cells correlated with their reprogramming efficiencies. We further identified metabolites that differ between iPSCs and ESCs, which revealed novel metabolic pathways that play a critical role in regulating somatic cell reprogramming. Our findings are the first to globally analyze the metabolome of iPSCs, and provide mechanistic insight into a new layer of regulation involved in inducing pluripotency, and in evaluating iPSC and ESC equivalence.
doi:10.1038/cr.2011.177
PMCID: PMC3252494  PMID: 22064701
reprogramming; iPS cells; metabolome; stem cells; metabolism
16.  Elimination of paternal mitochondria through the lysosomal degradation pathway in C. elegans 
Cell Research  2011;21(12):1662-1669.
In mammals, the inheritance of mitochondrion and its DNA (mtDNA) is strictly maternal, despite the fact that a sperm can inject up to 100 functional mitochondria into the oocyte during fertilization. The mechanisms responsible for the elimination of the paternal mitochondria remain largely unknown. We report here that this paternal mitochondrial elimination process is conserved in Caenorhabditis elegans, and that the lysosomal pathway actively participates in this process. Molecular and cell biological analyses indicate that in wild-type animals paternal mitochondria and mtDNA are destroyed within two hours after fertilization. In animals with compromised lysosomes, paternal mitochondria persist until late embryonic stages. Therefore, the lysosomal pathway plays an important role in degrading paternal mitochondria introduced into the oocyte during fertilization. Our study indicates that C. elegans is an excellent animal model for understanding and dissecting this conserved biological process critical for animal development and reproduction.
doi:10.1038/cr.2011.182
PMCID: PMC3234996  PMID: 22105480
lysosomal degradation; paternal mitochondria elimination; C. elegans; maternal inheritance; mitochondria DNA; fertilized oocyte
17.  Heterogeneity and plasticity of T helper cells 
Cell research  2009;20(1):4-12.
CD4 T helper (Th) cells play critical roles in adaptive immune responses. They recruit and activate other immune cells including B cells, CD8 T cells, macrophages, mast cells, neutrophils, eosinophils and basophils. Based on their functions, their pattern of cytokine secretion and their expression of specific transcription factors, Th cells, differentiated from naïve CD4 T cells, are classified into four major lineages, Th1, Th2, Th17 and T regulatory (Treg) cells, although other Th lineages may exist. Subsets of the same lineage may express different effector cytokines, reside at different locations or give rise to cells with different fates, whereas cells from different lineages may secrete common cytokines, such as IL-2, IL-9 and IL-10, resulting in massive heterogeneity of the Th cell population. In addition, the pattern of cytokine secretion may switch from that of one lineage toward another under certain circumstances, suggesting that Th cells are plastic. Tregs are also more heterogeneous and plastic than were originally thought. In this review, we summarize recent reports on heterogeneity and plasticity of Th cells, and discuss potential mechanisms and implications of such features that Th cells display.
doi:10.1038/cr.2009.138
PMCID: PMC3494736  PMID: 20010916
CD4; Tregs; T cell differentiation; transcription factors; cytokines
18.  Evidence for a critical role of gene occlusion in cell fate restriction 
Cell Research  2011;22(5):848-858.
The progressive restriction of cell fate during lineage differentiation is a poorly understood phenomenon despite its ubiquity in multicellular organisms. We recently used a cell fusion assay to define a mode of epigenetic silencing that we termed “occlusion”, wherein affected genes are silenced by cis-acting chromatin mechanisms irrespective of whether trans-acting transcriptional activators are present. We hypothesized that occlusion of lineage-inappropriate genes could contribute to cell fate restriction. Here, we test this hypothesis by introducing bacterial artificial chromosomes (BACs) – which are devoid of chromatin modifications necessary for occlusion – into mouse fibroblasts. We found that BAC transgenes corresponding to occluded endogenous genes are expressed in most cases, whereas BAC transgenes corresponding to silent but non-occluded endogenous genes are not expressed. This indicates that the cellular milieu in trans supports the expression of most occluded genes in fibroblasts, and that the silent state of these genes is solely the consequence of occlusion in cis. For the BAC corresponding to the occluded myogenic master regulator Myf5, expression of the Myf5 transgene on the BAC triggered fibroblasts to acquire a muscle-like phenotype. These results provide compelling evidence for a critical role of gene occlusion in cell fate restriction.
doi:10.1038/cr.2011.190
PMCID: PMC3297702  PMID: 22124232
cell fate restriction; occlusion; bacterial artificial chromosome
19.  GPR55 regulates cannabinoid 2 receptor-mediated responses in human neutrophils 
Cell Research  2011;21(10):1452-1469.
The directional migration of neutrophils towards inflammatory mediators, such as chemokines and cannabinoids, occurs via the activation of seven transmembrane G protein coupled receptors (7TM/GPCRs) and is a highly organized process. A crucial role for controlling neutrophil migration has been ascribed to the cannabinoid CB2 receptor (CB2R), but additional modulatory sites distinct from CB2R have recently been suggested to impact CB2R-mediated effector functions in neutrophils. Here, we provide evidence that the recently de-orphanized 7TM/GPCR GPR55 potently modulates CB2R-mediated responses. We show that GPR55 is expressed in human blood neutrophils and its activation augments the migratory response towards the CB2R agonist 2-arachidonoylglycerol (2-AG), while inhibiting neutrophil degranulation and reactive oxygen species (ROS) production. Using HEK293 and HL60 cell lines, along with primary neutrophils, we show that GPR55 and CB2R interfere with each other's signaling pathways at the level of small GTPases, such as Rac2 and Cdc42. This ultimately leads to cellular polarization and efficient migration as well as abrogation of degranulation and ROS formation in neutrophils. Therefore, GPR55 limits the tissue-injuring inflammatory responses mediated by CB2R, while it synergizes with CB2R in recruiting neutrophils to sites of inflammation.
doi:10.1038/cr.2011.60
PMCID: PMC3132458  PMID: 21467997
GPR55; CB2R; chemotaxis; ROS production; Rac2; Cdc42
20.  Revealing a steroid receptor ligand as a unique PPARγ agonist 
Cell Research  2011;22(4):746-756.
Peroxisome proliferator activated receptor gamma (PPARγ) regulates metabolic homeostasis and is a molecular target for antidiabetic drugs. We report here the identification of a steroid receptor ligand, RU-486, as an unexpected PPARγ agonist, thereby uncovering a novel signaling route for this steroid drug. Similar to rosiglitazone, RU-486 modulates the expression key PPARγ target genes and promotes adipocyte differentiation but with lower adipogenic activity. Structural and functional studies of receptor-ligand interactions reveal the molecular basis for a unique binding mode for RU-486 in the PPARγ ligand binding pocket with distinctive properties and epitopes, providing the molecular mechanisms for the discrimination of RU-486 from thiazolidinediones (TZDs) drugs. Our findings together indicate that steroid compounds may represent an alternative approach for designing non-thiazolidinedione PPARγ ligands in the treatment of insulin resistance.
doi:10.1038/cr.2011.162
PMCID: PMC3257359  PMID: 21986665
PPARγ; nuclear receptor; diabetes; crystal structure; steroid compound
21.  Essential role of DOT1L in maintaining normal adult hematopoiesis 
Cell Research  2011;21(9):1370-1373.
doi:10.1038/cr.2011.115
PMCID: PMC3166961  PMID: 21769133
22.  Bmi1 puSHHes reprogramming 
Cell Research  2011;21(9):1277-1278.
doi:10.1038/cr.2011.126
PMCID: PMC3193464
23.  BNIP3 is Essential for Mediating 6-thioguanine-and 5-fluorouracil-induced Autophagy Following DNA Mismatch Repair Processing 
Cell research  2010;20(6):665-675.
DNA mismatch repair (MMR) processes the chemically-induced mispairs following treatment with clinically important nucleoside analogs such as 6-thioguanine (6-TG) and 5-fluorouracil (5-FU). MMR processing of these drugs has been implicated in activation of a prolonged G2/M cell cycle arrest for repair and later induction of apoptosis and/or autophagy for irreparable DNA damage. In this study, we investigated the role of BNIP3 in the activation of autophagy and the temporal relationship between a G2/M cell cycle arrest and the activation of BNIP3-mediated autophagy following MMR processing of 6-TG and 5-FU. We found that BNIP3 protein levels are up-regulated in a MLH1 (MMR+)-dependent manner following 6-TG and 5-FU treatment. Subsequent siRNA-mediated BNIP3 knockdown abrogates 6-TG -induced autophagy. We also found that p53 knockdown or inhibition of mTOR activity by rapamycin cotreatment impairs 6-TG and 5-FU-induced up-regulation of BNIP3 protein levels and autophagy. Furthermore, suppression of Chk1 expression and a subsequent reduction in 6-TG-induced G2/M cell cycle arrest by Chk1 siRNA promotes the extent of 6-TG-induced autophagy. These findings suggest that BNIP3 mediates 6-TG- and 5-FU induced autophagy in a p53- and mTOR-dependent manner. Additionally, the duration of Chk1-activated G2/M cell cycle arrest determines the level of autophagy following MMR processing of these nucleoside analogs.
doi:10.1038/cr.2010.40
PMCID: PMC3430372  PMID: 20368736
BNIP3; p53; mTOR; autophagy; nucleoside analogs
24.  Fen1 mutations that specifically disrupt its interaction with PCNA cause aneuploidy-associated cancer 
Cell Research  2011;21(7):1052-1067.
DNA replication and repair are critical processes for all living organisms to ensure faithful duplication and transmission of genetic information. Flap endonuclease 1 (Fen1), a structure-specific nuclease, plays an important role in multiple DNA metabolic pathways and maintenance of genome stability. Human FEN1 mutations that impair its exonuclease activity have been linked to cancer development. FEN1 interacts with multiple proteins, including proliferation cell nuclear antigen (PCNA), to form various functional complexes. Interactions with these proteins are considered to be the key molecular mechanisms mediating FEN1's key biological functions. The current challenge is to experimentally demonstrate the biological consequence of a specific interaction without compromising other functions of a desired protein. To address this issue, we established a mutant mouse model harboring a FEN1 point mutation (F343A/F344A, FFAA), which specifically abolishes the FEN1/PCNA interaction. We show that the FFAA mutation causes defects in RNA primer removal and long-patch base excision repair, even in the heterozygous state, resulting in numerous DNA breaks. These breaks activate the G2/M checkpoint protein, Chk1, and induce near-tetraploid aneuploidy, commonly observed in human cancer, consequently elevating the transformation frequency. Consistent with this, inhibition of aneuploidy formation by a Chk1 inhibitor significantly suppressed the cellular transformation. WT/FFAA FEN1 mutant mice develop aneuploidy-associated cancer at a high frequency. Thus, this study establishes an exemplary case for investigating the biological significance of protein-protein interactions by knock-in of a point mutation rather than knock-out of a whole gene.
doi:10.1038/cr.2011.35
PMCID: PMC3129403  PMID: 21383776
FEN1; PCNA; Okazaki fragment maturation; long patch base excision repair; tetraploidy; aneuploidy; cancer
25.  Maximizing target protein ablation by integration of RNAi and protein knockout 
Cell Research  2011;21(7):1152-1154.
doi:10.1038/cr.2011.89
PMCID: PMC3129447  PMID: 21606956

Results 1-25 (113)