title: Expansion of the polyQ repeats in THAP11 forms intranuclear aggregation and causes cell G0/G1 arrest.
abstract: Polyglutamine diseases are a group of neurodegenerative disorders caused by expansion of a CAG repeat that encodes polyglutamine in each respective disease gene. The transcription factor THAP11, a member of THAP family, is involved in cell growth, ES cell pluripotency and embryogenesis. Previous studies suggest that THAP11 protein contains a 29-residue repeat polyglutamine motif and the number of polyglutamine ranges from 20 to 41 in Indian population. We have investigated the CAG numbers at the THAP11 locus in normal individuals and neurodegenerative disease patients of Chinese Han population and a 38Q expansion (THAP11(38Q)) was found in patients. Using fluorescence confocal-based cell imaging, THAP11(38Q) protein formed intranuclear inclusions easier than THAP11(29Q) in PC12 cells. Enhanced toxicity was investigated in THAP11(38Q)-expressing cells by growth inhibition and G0/G1 arrest. CREB-mediated transcription activity was inhibited by THAP11(38Q). The transcription factor, TBP, coactivator CBP, and chaperon protein, HSP70, could be recruited to THAP11(38Q). These results indicate that expansion of the polyglutamine in THAP11 forms intracellular aggregation and is toxic in PC12 cells, suggesting a putative role of THAP11 in polyglutamine disease.
authors.affiliation: Beijing Institute of Radiation Medicine, Beijing, 100850, China.
authors.forename: Rong-Hua
authors.initials: RH
authors.lastname: Yin
authors.forename: Yang
authors.initials: Y
authors.lastname: Li
authors.forename: Fan
authors.initials: F
authors.lastname: Yang
authors.forename: Yi-Qun
authors.initials: YQ
authors.lastname: Zhan
authors.forename: Miao
authors.initials: M
authors.lastname: Yu
authors.forename: Chang-Hui
authors.initials: CH
authors.lastname: Ge
authors.forename: Wang-Xiang
authors.initials: WX
authors.lastname: Xu
authors.forename: Liu-Jun
authors.initials: LJ
authors.lastname: Tang
authors.forename: Xiao-Hui
authors.initials: XH
authors.lastname: Wang
authors.forename: Biao
authors.initials: B
authors.lastname: Chen
authors.forename: Yang
authors.initials: Y
authors.lastname: Yang
authors.forename: Jian-Jie
authors.initials: JJ
authors.lastname: Li
authors.forename: Chang-Yan
authors.initials: CY
authors.lastname: Li
authors.forename: Xiao-Ming
authors.initials: XM
authors.lastname: Yang
mesh_terms: D000818:Animals; D002460:Cell Line; D049109:Cell Proliferation / Q000235:genetics; D017362:Cyclic AMP Response Element-Binding Protein / Q000037:antagonists & inhibitors / Q000235:genetics; D059585:G1 Phase Cell Cycle Checkpoints; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism; D006801:Humans; D045586:Intranuclear Inclusion Bodies / Q000473:pathology*; D016716:PC12 Cells; D010446:Peptide Fragments / Q000378:metabolism; D010455:Peptides / Q000235:genetics*; D011110:Polymorphism, Genetic / Q000235:genetics; D051381:Rats; D012097:Repressor Proteins / Q000235:genetics*; D012795:Sialoglycoproteins / Q000378:metabolism; D020754:Spinocerebellar Ataxias / Q000235:genetics*; D035181:TATA-Box Binding Protein / Q000378:metabolism
chemical_list: C115163:CREB1 protein, human; D017362:Cyclic AMP Response Element-Binding Protein; D018840:HSP70 Heat-Shock Proteins; D010446:Peptide Fragments; D010455:Peptides; D012097:Repressor Proteins; D012795:Sialoglycoproteins; D035181:TATA-Box Binding Protein; C509817:TBP protein, human; C498470:THAP11 protein, human; C571744:bone sialoprotein (35-62), human; C097188:polyglutamine
keywords: THAP11; cell cycle arrest; intracellular aggregation; polyglutamine expansion