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A biotin switch-based proteomics approach identifies 14-3-3ζ as a target of Sirt1 in the metabolic regulation of caspase-2.

Publication ,  Journal Article
Andersen, JL; Thompson, JW; Lindblom, KR; Johnson, ES; Yang, C-S; Lilley, LR; Freel, CD; Moseley, MA; Kornbluth, S
Published in: Mol Cell
September 2, 2011

While lysine acetylation in the nucleus is well characterized, comparatively little is known about its significance in cytoplasmic signaling. Here we show that inhibition of the Sirt1 deacetylase, which is primarily cytoplasmic in cancer cell lines, sensitizes these cells to caspase-2-dependent death. To identify relevant Sirt1 substrates, we developed a proteomics strategy, enabling the identification of a range of putative substrates, including 14-3-3ζ, a known direct regulator of caspase-2. We show here that inhibition of Sirtuin activity accelerates caspase activation and overrides caspase-2 suppression by nutrient abundance. Furthermore, 14-3-3ζ is acetylated prior to caspase activation, and supplementation of Xenopus egg extract with glucose-6-phosphate, which promotes caspase-2/14-3-3ζ binding, enhances 14-3-3ζ-directed Sirtuin activity. Conversely, inhibiting Sirtuin activity promotes14-3-3ζ dissociation from caspase-2 in both egg extract and human cultured cells. These data reveal a role for Sirt1 in modulating apoptotic sensitivity, in response to metabolic changes, by antagonizing 14-3-3ζ acetylation.

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Published In

Mol Cell

DOI

EISSN

1097-4164

Publication Date

September 2, 2011

Volume

43

Issue

5

Start / End Page

834 / 842

Location

United States

Related Subject Headings

  • Sirtuin 1
  • Proteomics
  • Humans
  • Developmental Biology
  • Cytoplasm
  • Cell Line, Tumor
  • Cell Death
  • Caspase 2
  • Biotin
  • Apoptosis
 

Citation

APA
Chicago
ICMJE
MLA
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Andersen, J. L., Thompson, J. W., Lindblom, K. R., Johnson, E. S., Yang, C.-S., Lilley, L. R., … Kornbluth, S. (2011). A biotin switch-based proteomics approach identifies 14-3-3ζ as a target of Sirt1 in the metabolic regulation of caspase-2. Mol Cell, 43(5), 834–842. https://doi.org/10.1016/j.molcel.2011.07.028
Andersen, Joshua L., J Will Thompson, Kelly R. Lindblom, Erika S. Johnson, Chih-Sheng Yang, Lauren R. Lilley, Christopher D. Freel, M Arthur Moseley, and Sally Kornbluth. “A biotin switch-based proteomics approach identifies 14-3-3ζ as a target of Sirt1 in the metabolic regulation of caspase-2.Mol Cell 43, no. 5 (September 2, 2011): 834–42. https://doi.org/10.1016/j.molcel.2011.07.028.
Andersen JL, Thompson JW, Lindblom KR, Johnson ES, Yang C-S, Lilley LR, et al. A biotin switch-based proteomics approach identifies 14-3-3ζ as a target of Sirt1 in the metabolic regulation of caspase-2. Mol Cell. 2011 Sep 2;43(5):834–42.
Andersen, Joshua L., et al. “A biotin switch-based proteomics approach identifies 14-3-3ζ as a target of Sirt1 in the metabolic regulation of caspase-2.Mol Cell, vol. 43, no. 5, Sept. 2011, pp. 834–42. Pubmed, doi:10.1016/j.molcel.2011.07.028.
Andersen JL, Thompson JW, Lindblom KR, Johnson ES, Yang C-S, Lilley LR, Freel CD, Moseley MA, Kornbluth S. A biotin switch-based proteomics approach identifies 14-3-3ζ as a target of Sirt1 in the metabolic regulation of caspase-2. Mol Cell. 2011 Sep 2;43(5):834–842.
Journal cover image

Published In

Mol Cell

DOI

EISSN

1097-4164

Publication Date

September 2, 2011

Volume

43

Issue

5

Start / End Page

834 / 842

Location

United States

Related Subject Headings

  • Sirtuin 1
  • Proteomics
  • Humans
  • Developmental Biology
  • Cytoplasm
  • Cell Line, Tumor
  • Cell Death
  • Caspase 2
  • Biotin
  • Apoptosis