title: MCPH1/BRIT1 represses transcription of the human telomerase reverse transcriptase gene.
abstract: MCPH1, a repressor of human telomerase reverse transcriptase (hTERT) function, is implicated in cellular immortalization. But little is known about how MCPH1 represses telomerase activity. In this study, to determine the mechanism by which MCPH1 regulates hTERT gene expression, we examined the role of MCPH1 in regulating the hTERT promoter in vitro. Co-transfection of the hTERT promoter with MCPH1 in Hela cells could inhibit the hTERT promoter activity. The EMSA assay demonstrated that MCPH1 could bind to the proximal hTERT promoter. Overexpression of MCPH1 could repress telomerase activity, and the repression was abolished by knocking down the MCPH1 expression using siRNA in U2OS cells. We propose that MCPH1 functions as a transcriptional repressor of hTERT in vitro. Since the activation of telomerase, widely observed in human tumor cell lines, is a critical step in tumorigenesis, our findings provide new insights into delineating the tumor-suppressing function of MCPH1 through its down-regulation of hTERT/telomerase expression.
authors.affiliation: State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, PR China.
authors.forename: Lei
authors.initials: L
authors.lastname: Shi
authors.forename: Ming
authors.initials: M
authors.lastname: Li
authors.forename: Bing
authors.initials: B
authors.lastname: Su
mesh_terms: D018797:Cell Cycle Proteins; D003598:Cytoskeletal Proteins; D024202:Electrophoretic Mobility Shift Assay; D015971:Gene Expression Regulation, Enzymologic; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D034741:RNA, Small Interfering / Q000378:metabolism; D012097:Repressor Proteins / Q000378:metabolism*; D019098:Telomerase / Q000235:genetics*; D014158:Transcription, Genetic
chemical_list: D018797:Cell Cycle Proteins; D003598:Cytoskeletal Proteins; C460645:MCPH1 protein, human; D009419:Nerve Tissue Proteins; D034741:RNA, Small Interfering; D012097:Repressor Proteins; C509186:TERT protein, human; D019098:Telomerase