title: Human nuclear clusterin mediates apoptosis by interacting with Bcl-XL through C-terminal coiled coil domain.
abstract: Clusterin (CLU), a glycoprotein, is involved in apoptosis, producing two alternatively spliced isoforms in various cell types. The pro-apoptotic CLU appears to be a nuclear isoform (nuclear clusterin; nCLU), and the secretory CLU (sCLU) is thought to be anti-apoptotic. The detailed molecular mechanism of nCLU as a pro-apoptotic molecule has not yet been clear. In the current study, overexpressed nCLU induced apoptosis in human kidney cells. Biochemical studies revealed that nCLU sequestered Bcl-XL via a putative BH3 motif in the C-terminal coiled coil (CC2) domain, releasing Bax, and promoted apoptosis accompanied by activation of caspase-3 and cytochrome c release. These results suggest a novel mechanism of apoptosis mediated by nCLU as a pro-apoptotic molecule.
authors.affiliation: Department of Anatomy and Neurobiology, Medical Research Center for Neural Dysfunction, School of Medicine, Gyeongsang National University, Jinju, Gyeongnam, South Korea.
authors.forename: Nayoung
authors.initials: N
authors.lastname: Kim
authors.forename: Jae Cheal
authors.initials: JC
authors.lastname: Yoo
authors.forename: Jae Yoon
authors.initials: JY
authors.lastname: Han
authors.forename: Eun Mi
authors.initials: EM
authors.lastname: Hwang
authors.forename: Yoon Sook
authors.initials: YS
authors.lastname: Kim
authors.forename: Eun Young
authors.initials: EY
authors.lastname: Jeong
authors.forename: Choong-Hyun
authors.initials: CH
authors.lastname: Sun
authors.forename: Gwan-Su
authors.initials: GS
authors.lastname: Yi
authors.forename: Gu Seob
authors.initials: GS
authors.lastname: Roh
authors.forename: Hyun Joon
authors.initials: HJ
authors.lastname: Kim
authors.forename: Sang Soo
authors.initials: SS
authors.lastname: Kang
authors.forename: Gyeong Jae
authors.initials: GJ
authors.lastname: Cho
authors.forename: Jae-Yong
authors.initials: JY
authors.lastname: Park
authors.forename: Wan Sung
authors.initials: WS
authors.lastname: Choi
mesh_terms: D020816:Amino Acid Motifs / Q000235:genetics; D000595:Amino Acid Sequence; D017209:Apoptosis / Q000235:genetics; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000235:genetics; D051152:Clusterin / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D057809:HEK293 Cells; D006801:Humans; D015603:Keratinocytes / Q000166:cytology / Q000502:physiology; D008297:Male; D008969:Molecular Sequence Data; D011471:Prostatic Neoplasms; D054730:Protein Interaction Domains and Motifs / Q000235:genetics; D017434:Protein Structure, Tertiary / Q000502:physiology; D051020:bcl-X Protein / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
chemical_list: C494811:BCL2L1 protein, human; C495242:CLU protein, human; D051152:Clusterin; D051020:bcl-X Protein