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

• Published in: Biochemical and biophysical research communications Vol. 412; no. 3; pp. 454 - 459
• Main Authors: Jin, Hyung-Seung, Park, Hyung-Sun, Shin, Jun-Ha, Kim, Dong-Hwan, Jun, Sung-Hun, Lee, Chang-Jun, Lee, Tae H.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 02.09.2011
• Subjects: 60 APPLIED LIFE SCIENCES; Active Transport, Cell Nucleus; APOPTOSIS; Cell Nucleus - metabolism; cIAP1; cIAP2; CYTOPLASM; DESORPTION; HEK293 Cells; HeLa Cells; Humans; IAP regulator; INHIBITION; Inhibitor of Apoptosis Proteins - metabolism; IONIZATION; LASERS; RECEPTORS; TIME-OF-FLIGHT METHOD; TNF Receptor-Associated Factor 2 - metabolism; TRAF2; TRANSCRIPTION; Transcription Factors - metabolism; TRANSLOCATION; Vgl-4; X-Linked Inhibitor of Apoptosis Protein; XIAP; MALDI-TOF; cIAP2; IAP; cIAP1; XIAP; BIR; TRAF2; XAF1; Vgl-4; IAP regulator
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2011.07.117

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