A novel inhibitor of apoptosis protein (IAP)-interacting protein, Vestigial-like (Vgl)-4, counteracts apoptosis-inhibitory function of IAPs by nuclear sequestration

Journal Article · Fri Sep 02 04:00:00 EDT 2011 · Biochemical and Biophysical Research Communications

DOI:https://doi.org/10.1016/J.BBRC.2011.07.117· OSTI ID:22207478

Jin, Hyung-Seung; Park, Hyung-Sun ^[1]; Shin, Jun-Ha ^[2]; Kim, Dong-Hwan ^[1]; Jun, Sung-Hun; Lee, Chang-Jun ^[1]

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1. Department of Systems Biology, College of Life Science and Biotechnology, Yonsei University, Yonsei-ro 50, Seodaemoon-gu, Seoul 120-749 (Korea, Republic of)
2. Department of Biotechnology, College of Life Science and Biotechnology, Yonsei University, Yonsei-ro 50, Seodaemoon-gu, Seoul 120-749 (Korea, Republic of)

Highlights: {yields} We identified a new IAP binding protein Vgl-4. {yields} Vgl-4 is expressed mainly in the nucleus and triggers a relocalization of IAPs from the cytoplasm to the nucleus. {yields} Vgl-4-mediated IAP nuclear localization was blocked by TRAF2 coexpression. {yields} Vgl-4 suppresses the ability of IAPs to prevent cell death, however TRAF2 can revere the effect of Vgl-4. {yields} Vgl-4 functions as an IAP regulator by binding to IAPs and altering their sub-cellular localization. -- 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 TNF{alpha}-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.

• OSTI ID: 22207478
• Journal Information: Biochemical and Biophysical Research Communications, Journal Name: Biochemical and Biophysical Research Communications Journal Issue: 3 Vol. 412; ISSN 0006-291X; ISSN BBRCA9
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
APOPTOSIS
CYTOPLASM
DESORPTION
INHIBITION
IONIZATION
LASERS
RECEPTORS
TIME-OF-FLIGHT METHOD
TRANSCRIPTION
TRANSLOCATION