The carboxyl-terminal tail of Noxa protein regulates the stability of Noxa and Mcl-1

Xiaming Pang, Jingjing Zhang, Hernando Lopez, Yushu Wang, Wenyang Li, Katelyn L. O'Neill, Jacquelynn J.D. Evans, Nicholas M. George, Jianhong Long, Yi Chen, Xu Luo

Research output: Contribution to journalArticlepeer-review

22 Scopus citations

Abstract

The BH3-only protein Noxa is a critical mediator of apoptosis and functions primarily by sequestering/inactivating the antiapoptotic Bcl-2 family protein Mcl-1. Although Noxa is a highly labile protein, recent studies suggested that it is degraded by the proteasome in a ubiquitylation-independent manner. In the present study, we investigated the mechanism of Noxa degradation and its ability to regulate the stability of Mcl-1. We found that the ubiquitylation- independent degradation of Noxa does not require a physical association with Mcl-1. A short stretch of amino acid residues in the C-terminal tail was found to mediate the proteasome-dependent degradation of Noxa. Ectopic placement of this degron was able to render other proteins unstable. Surprisingly, mutation of this sequence not only attenuated the rapid degradation of Noxa, but also stabilized endogenous Mcl-1 through the BH3-mediated direct interaction. Together, these results suggest that the C-terminal tail of Noxa regulates the stability of both Noxa and Mcl-1.

Original languageEnglish (US)
Pages (from-to)17802-17811
Number of pages10
JournalJournal of Biological Chemistry
Volume289
Issue number25
DOIs
StatePublished - Jun 20 2014

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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