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author:("Chen, xiaohui")
1.  RXRα and LXR activate two promoters in placenta- and tumor-specific expression of PLAC1 
Placenta  2011;32(11):877-884.
PLAC1 expression, first characterized as restricted to developing placenta among normal tissues, is also found in a wide range of tumors and transformed cell lines. To understand the basis for its unusual expression profile, we have analyzed the gene structure and its mode of transcription. We find that the gene has a hitherto unique feature, with two promoters, P1 and P2, separated by 105 kb. P2 has been described before. Here we define P1 and show that it and P2 are activated by RXRα in conjunction with LXRα or LXRβ. In placenta, P2 is the preferred promoter, whereas various tumor cell lines tend to express predominantly either one or the other promoter. Furthermore, when each promoter is fused to a luciferase reporter gene and transfected into cancer cell lines, the promoter corresponding to the more active endogenous promoter is preferentially transcribed. Joint expression of activating nuclear receptors can partially account for the restricted expression of PLAC1 in placenta, and may be co-opted for preferential P1 or P2 PLAC1 expression in various tumor cells.
PMCID: PMC3210379  PMID: 21937108
2.  Proteomic analysis of SRA01/04 transfected with wild-type and mutant HSF4b identified from a Chinese congenital cataract family 
Molecular Vision  2012;18:694-704.
Congenital cataracts account for about 10% of cases of childhood blindness. Heat shock transcription factor 4 (HSF4) is related with human autosomal dominant lamellar and Marner cataracts; a T→C transition at nucleotide 348 was found in a large Chinese cataract family. The aim of this study was to analyze the unique role of HSF4b and the mutation of HSF4b.
The isobaric tags for relative and absolute quantification (iTRAQ), coupled with the two-dimensional liquid chromatography-tandem mass spectrometry (2D LC-MS/MS) technique, was used to identify and quantify differential proteomes in human lens epithelial cell lines SRA 01/04 expressing wild-type and mutant HSF4b.
A total of 104 unique proteins were identified from the human lens epithelial cell lines SRA 01/04. Apart from the proteins due to the effect of the pcDNA3.1 vector, the wild-type and mutant HSF4b led to 23 differentially expressed proteins, of which four were histone proteins and three were ribosomal proteins. The T→C transition at nucleotide 348 in HSF4b led to 18 differentially expressed proteins in SRA 01/04, among which serpin H1 precursor, heat shock protein beta-1, and stress-70 protein belong to heat shock protein families. The up- or down-regulated proteins were functionally analyzed using Ingenuity Pathways Analysis (IPA) to interpret the interaction network and predominant canonical pathways involved in these differentially expressed proteins.
A multitude of differentially expressed proteins was found to be associated with HSF4b and a T→C transition at nucleotide 348 in HSF4b. The proteins interacted directly or indirectly with each other, and they may provide clues as to how HSF4b modulates protein expression in the lens epithelial cells of SRA 01/04. Although further investigation is required, the results may provide some new clues to the transcriptional mechanism of HSF4b and cataract formation.
PMCID: PMC3324350  PMID: 22509099
3.  Tumour suppressor SIRT3 deacetylates and activates manganese superoxide dismutase to scavenge ROS 
EMBO Reports  2011;12(6):534-541.
Tumour suppressor SIRT3 deacetylates and activates manganese superoxide dismutase to scavenge ROS
Mitochondria manganese superoxide dismutase (SOD2) is a major antioxidant enzyme associated with several diseases. This study shows that SOD2 is inhibited by acetylation and activated by SIRT3-mediated deacetylation in response to reactive oxygen species (ROS).
Mitochondria manganese superoxide dismutase (SOD2) is an important antioxidant enzyme, deficiency of which is associated with various human diseases. The known primary regulation of SOD2 is through transcriptional activation. Here, we report that SOD2 is acetylated at Lys 68 and that this acetylation decreases SOD2 activity. Mitochondrial deacetylase SIRT3 binds to, deacetylates and activates SOD2. Increase of reactive oxygen species (ROS) levels stimulates SIRT3 transcription, leading to SOD2 deacetylation and activation. SOD2-mediated ROS reduction is synergistically increased by SIRT3 co-expression, but is cancelled by SIRT3 depletion. These results reveal a new post-translational regulation of SOD2 by means of acetylation and SIRT3-dependent deacetylation in response to oxidative stress.
PMCID: PMC3128277  PMID: 21566644
acetylation; ROS; SIRT3; SOD2
4.  Proteomic analysis of differential proteins in pancreatic carcinomas: Effects of MBD1 knock-down by stable RNA interference 
BMC Cancer  2008;8:121.
Methyl-CpG binding domain protein 1 (MBD1), a suppressor of gene transcription, may be involved in inactivation of tumor suppressor genes during tumorigenesis. Over-expression of MBD1 has been reported in human pancreatic carcinomas.
In this study, we established a MBD1-knock-down pancreatic cancer cell line (BxPC-3) using stable RNA interference, to compare the proteomic changes between control and MBD1-knock-down cells using two-dimensional gel electrophoresis and mass spectrometry.
We identified five proteins that were up-regulated and nine proteins that were down-regulated. Most of the identified proteins are involved in tumorigenesis, some are prognostic biomarkers for human malignant tumors.
Our data suggest that these differential proteins may be associated with the function of MBD1, and provide some insight into the functional mechanism of MBD1 in the development of pancreatic cancer.
PMCID: PMC2386481  PMID: 18445260
5.  Mammalian Sir2 Homolog SIRT3 Regulates Global Mitochondrial Lysine Acetylation▿ †  
Molecular and Cellular Biology  2007;27(24):8807-8814.
Homologs of the Saccharomyces cerevisiae Sir2 protein, sirtuins, promote longevity in many organisms. Studies of the sirtuin SIRT3 have so far been limited to cell culture systems. Here, we investigate the localization and function of SIRT3 in vivo. We show that endogenous mouse SIRT3 is a soluble mitochondrial protein. To address the function and relevance of SIRT3 in the regulation of energy metabolism, we generated and phenotypically characterized SIRT3 knockout mice. SIRT3-deficient animals exhibit striking mitochondrial protein hyperacetylation, suggesting that SIRT3 is a major mitochondrial deacetylase. In contrast, no mitochondrial hyperacetylation was detectable in mice lacking the two other mitochondrial sirtuins, SIRT4 and SIRT5. Surprisingly, despite this biochemical phenotype, SIRT3-deficient mice are metabolically unremarkable under basal conditions and show normal adaptive thermogenesis, a process previously suggested to involve SIRT3. Overall, our results extend the recent finding of lysine acetylation of mitochondrial proteins and demonstrate that SIRT3 has evolved to control reversible lysine acetylation in this organelle.
PMCID: PMC2169418  PMID: 17923681

Results 1-5 (5)