Dual role of JNK1-mediated phosphorylation of Bcl-2 in autophagy and apoptosis regulation

Yongjie Wei, Sangila Sinha, Beth Levine

Research output: Contribution to journalArticle

227 Citations (Scopus)

Abstract

Autophagy and apoptosis are fundamental cellular pathways that are both regulated by JNK-mediated Bcl-2 phosphorylation. Several years ago, JNK-mediated Bcl-2 phosphorylation was shown to interfere with its binding to proapoptotic BH3 domain-containing proteins such as Bax and recently, our laboratory demonstrated that JNK1-mediated Bcl-2 phosphorylation interferes with its binding to the proautophagy BH3 domain-containing protein Beclin 1. Here, we examined the kinetic relationship between Bcl-2 phosphorylation, Bcl-2-Beclin 1 interactions, Bcl-2-Bax interactions, and caspase 3 activation during nutrient starvation. We found that after a short period of nutrient deprivation (4 hours), a small amount of Bcl-2 phosphorylation dissociates Bcl-2 from the Bcl-2-Beclin 1 complex but not from the Bcl-2-Bax complex. After 16 hours of nutrient deprivation, Bcl-2 phosphorylation reaches maximal levels, the Bcl-2-Bax complex is disrupted, and active caspase 3 is detected, indicating the initiation of apoptosis. Based on this result, we propose a speculative model for understanding the interrelationship between autophagy and apoptosis regulated by JNK1-mediated Bcl-2 phosphorylation. According to this model, rapid Bcl-2 phosphorylation may occur initially to promote cell survival by disrupting the Bcl-2-Beclin 1 complex and activating autophagy. At a certain point when autophagy is no longer able to keep the cell alive, Bcl-2 phosphorylation might then serve to inactivate its antiapoptotic function.

Original languageEnglish (US)
Pages (from-to)949-951
Number of pages3
JournalAutophagy
Volume4
Issue number7
StatePublished - Oct 1 2008

Fingerprint

Autophagy
Phosphorylation
Apoptosis
Food
Caspase 3
Starvation
Cell Survival
Beclin-1

Keywords

  • Apoptosis
  • Autophagy
  • Bax
  • Bcl-2
  • Caspase 3
  • JNK1
  • Nutrient starvation

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology

Cite this

Dual role of JNK1-mediated phosphorylation of Bcl-2 in autophagy and apoptosis regulation. / Wei, Yongjie; Sinha, Sangila; Levine, Beth.

In: Autophagy, Vol. 4, No. 7, 01.10.2008, p. 949-951.

Research output: Contribution to journalArticle

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