Interaction and stabilization of X-linked inhibitor of apoptosis by Raf-1 protein kinase

  • Authors:
    • Song Tian
    • Rajshree R. Mewani
    • Deepak Kumar
    • Bihua Li
    • Malika T. Danner
    • Imran Ahmad
    • Aquilur Rahman
    • Vicente Notario
    • Anatoly Dritschilo
    • Usha N. Kasid
    • Prafulla C. Gokhale
  • View Affiliations

  • Published online on: October 1, 2006     https://doi.org/10.3892/ijo.29.4.861
  • Pages: 861-867
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Abstract

Raf-1 serine/threonine protein kinase plays an important role in cell growth, differentiation and cell survival. Recent reports using c-raf-1 gene-knockouts have observed MEK/ERK independent functions of Raf-1 in cell survival and protection from apoptosis. Raf-1 has also been shown to be involved in counteracting specific apoptotic pathways by restraining caspase activation, although the precise mechanism is unknown. XIAP is a potent inhibitor of apoptosis that blocks both the mitochondria and death receptor mediated pathways of apoptosis by directly binding to and inhibiting the initiator and effector caspases. In our efforts to understand the mechanism by which Raf-1 inhibits caspase activation, we discovered a novel interaction between Raf-1 and XIAP. In this study, we describe the physical interaction between Raf-1 and XIAP in vitro and in vivo in mammalian cells. We also demonstrate that Raf-1 phosphorylates XIAP in vitro and in vivo. Additionally, Raf-1 prevents XIAP degradation in response to different apoptotic triggers. Our studies identify XIAP as a new substrate of Raf-1 and provide potentially important insight into mechanisms underlying Raf-1 effects on cell survival.

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October 2006
Volume 29 Issue 4

Print ISSN: 1019-6439
Online ISSN:1791-2423

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APA
Tian, S., Mewani, R.R., Kumar, D., Li, B., Danner, M.T., Ahmad, I. ... Gokhale, P.C. (2006). Interaction and stabilization of X-linked inhibitor of apoptosis by Raf-1 protein kinase. International Journal of Oncology, 29, 861-867. https://doi.org/10.3892/ijo.29.4.861
MLA
Tian, S., Mewani, R. R., Kumar, D., Li, B., Danner, M. T., Ahmad, I., Rahman, A., Notario, V., Dritschilo, A., Kasid, U. N., Gokhale, P. C."Interaction and stabilization of X-linked inhibitor of apoptosis by Raf-1 protein kinase". International Journal of Oncology 29.4 (2006): 861-867.
Chicago
Tian, S., Mewani, R. R., Kumar, D., Li, B., Danner, M. T., Ahmad, I., Rahman, A., Notario, V., Dritschilo, A., Kasid, U. N., Gokhale, P. C."Interaction and stabilization of X-linked inhibitor of apoptosis by Raf-1 protein kinase". International Journal of Oncology 29, no. 4 (2006): 861-867. https://doi.org/10.3892/ijo.29.4.861