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Bak apoptotic function is not directly regulated by phosphorylation.

Authors
  • Tran, V H1
  • Bartolo, R
  • Westphal, D
  • Alsop, A
  • Dewson, G
  • Kluck, R M
  • 1 Molecular Genetics of Cancer Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia.
Type
Published Article
Journal
Cell Death and Disease
Publisher
Springer Nature
Publication Date
Jan 10, 2013
Volume
4
Identifiers
DOI: 10.1038/cddis.2012.191
PMID: 23303126
Source
Medline
License
Unknown

Abstract

During apoptosis, Bak and Bax permeabilize the mitochondrial outer membrane by undergoing major conformational change and oligomerization. This activation process in Bak is reported to require dephosphorylation of tyrosine-108 close to an activation trigger site. To investigate how dephosphorylation of Bak contributes to its activation and conformational change, one-dimensional isoelectric focusing (1D-IEF) and mutagenesis was used to monitor Bak phosphorylation. On 1D-IEF, Bak extracted from a range of cell types migrated as a single band near the predicted isoelectric point of 5.6 both before and after phosphatase treatment, indicating that Bak is not significantly phosphorylated at any residue. In contrast, three engineered 'phosphotagged' Bak variants showed a second band at lower pI, indicating phosphorylation. Apoptosis induced by several stimuli failed to alter Bak pI, indicating little change in phosphorylation status. In addition, alanine substitution of tyrosine-108 and other putative phosphorylation sites failed to enhance Bak activation or pro-apoptotic function. In summary, Bak is not significantly phosphorylated at any residue, and Bak activation during apoptosis does not require dephosphorylation.

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