Multisite phosphorylation regulates Bim stability and apoptotic activity
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UMass Chan Affiliations
Program in Molecular MedicineDocument Type
Journal ArticlePublication Date
2008-05-23
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The proapoptotic BH3-only protein Bim is established to be an important mediator of signaling pathways that induce cell death. Multisite phosphorylation of Bim by several members of the MAP kinase group is implicated as a regulatory mechanism that controls the apoptotic activity of Bim. To test the role of Bim phosphorylation in vivo, we constructed mice with a series of mutant alleles that express phosphorylation-defective Bim proteins. We show that mutation of the phosphorylation site Thr-112 causes decreased binding of Bim to the antiapoptotic protein Bcl2 and can increase cell survival. In contrast, mutation of the phosphorylation sites Ser-55, Ser-65, and Ser-73 can cause increased apoptosis because of reduced proteasomal degradation of Bim. Together, these data indicate that phosphorylation can regulate Bim by multiple mechanisms and that the phosphorylation of Bim on different sites can contribute to the sensitivity of cellular apoptotic responses.Source
Mol Cell. 2008 May 23;30(4):415-25. doi: 10.1016/j.molcel.2008.03.025. Link to article on publisher's siteDOI
10.1016/j.molcel.2008.03.025Permanent Link to this Item
http://hdl.handle.net/20.500.14038/28340PubMed ID
18498746Related Resources
Link to Article in PubMedae974a485f413a2113503eed53cd6c53
10.1016/j.molcel.2008.03.025