BAD is a pro-survival factor prior to activation of its pro-apoptotic function

Young Seo So, Ying Bei Chen, Iva Ivamovska, Ann M. Ranger, Suk J. Hong, Valina L. Dawson, Stanley J. Korsmeyer, David S. Bellows, Yihru Fannjiang, J. Marie Hardwick

Research output: Contribution to journalArticlepeer-review

Abstract

The mammalian BAD protein belongs io the BH3-only subgroup of the BCL-2 family. In contrast to its known pro-apoptotic function, we found that endogenous and overespressed BADL can inhibit cell death in neurons and other cell types. Several mechanisms regulate the conversion of BAD from an anti-death to a pro-death factor, including alternative splicing that produces the N-terminally truncated BADS. In addition, caspases convert BADL into a pro-death fragment that resembles the short splice variant. The caspase site that is selectively cleaved during cell death following growth factor (interleuldn-3) withdrawal is conserved between human and murine BAD. A second cleavage site that is required for murine BAD to promote death following Sindbis virus infection, γ-irradiation, and staurosporine treatment is not conserved in human BAD, consistent with the inability of human BAD to promote death with these stimuli. However, loss of the BAD N terminus by any mechanism is not always sufficient to activate its pro-death activity, suggesting that the N terminus is a regulatory domain rather than an anti-death domain. These findings suggest that BAD is more than an inert death factor in healthy cells; it is also a pro-survival factor, prior to its role in promoting cell death.

Original languageEnglish (US)
Pages (from-to)42240-42249
Number of pages10
JournalJournal of Biological Chemistry
Volume279
Issue number40
DOIs
StatePublished - Oct 1 2004

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Fingerprint

Dive into the research topics of 'BAD is a pro-survival factor prior to activation of its pro-apoptotic function'. Together they form a unique fingerprint.

Cite this