title: A novel inhibitor of apoptosis protein (IAP)-interacting protein, Vestigial-like (Vgl)-4, counteracts apoptosis-inhibitory function of IAPs by nuclear sequestration.
abstract: The inhibitors of apoptosis proteins (IAP), which include cIAP1, cIAP2 and XIAP, suppress apoptosis through the inhibition of caspases, and the activity of IAPs is regulated by a variety of IAP-binding proteins. Herein, we report the identification of a Vestigial-like 4 (Vgl-4), which functions as a transcription cofactor in cardiac myocytes, as a new IAP binding protein. Vgl-4 is expressed predominantly in the nucleus and its overexpression triggers a relocalization of IAPs from the cytoplasm to the nucleus. cIAP1/2-interacting protein TRAF2 (TNF receptor-associated factor 2) prevented the Vgl-4-driven nuclear localization of cIAP2. Accordingly, the forced relocation of IAPs to the nucleus by Vgl-4 significantly reduced their ability to prevent Bax- and TNFα-induced apoptosis, which can be recovered by co-expression with TRAF2. Our results suggest that Vgl-4 may play a role in the apoptotic pathways by regulating translocation of IAPs between different cell compartments.
authors.affiliation: Department of Systems Biology, College of Life Science and Biotechnology, Yonsei University, Yonsei-ro 50, Seodaemoon-gu, Seoul 120-749, Republic of Korea.
authors.forename: Hyung-Seung
authors.initials: HS
authors.lastname: Jin
authors.forename: Hyung-Sun
authors.initials: HS
authors.lastname: Park
authors.forename: Jun-Ha
authors.initials: JH
authors.lastname: Shin
authors.forename: Dong-Hwan
authors.initials: DH
authors.lastname: Kim
authors.forename: Sung-Hun
authors.initials: SH
authors.lastname: Jun
authors.forename: Chang-Jun
authors.initials: CJ
authors.lastname: Lee
authors.forename: Tae H
authors.initials: TH
authors.lastname: Lee
mesh_terms: D021581:Active Transport, Cell Nucleus; D017209:Apoptosis; D002467:Cell Nucleus / Q000378:metabolism*; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000378:metabolism*; D047992:TNF Receptor-Associated Factor 2 / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism*; D051636:X-Linked Inhibitor of Apoptosis Protein
chemical_list: D051034:Inhibitor of Apoptosis Proteins; D047992:TNF Receptor-Associated Factor 2; D014157:Transcription Factors; C488533:VGLL4 protein, human; D051636:X-Linked Inhibitor of Apoptosis Protein