Threonine 48 in the BIR domain of survivin is critical to its mitotic and anti-apoptotic activities and can be phosphorylated by CK2 in vitro

Cell Cycle. 2011 Feb 1;10(3):538-48. doi: 10.4161/cc.10.3.14758. Epub 2011 Feb 1.

Abstract

In this study we report that the protein kinase CK2 phosphorylates survivin specifically on threonine 48 (T48) within its BIR domain, and that T48 is critical to both the mitotic and anti-apoptotic roles of survivin. Interestingly, during mitosis T48 mutants localise normally, but are unable to support cell growth when endogenous survivin is removed by siRNA. In addition, while overexpression of survivin normally confers inhibition of TRAIL-mediated apoptosis, this protection is abolished by mutation of T48. Furthermore in interphase cells depletion of endogenous survivin causes redistribution of T48 mutants from the cytoplasm to the nucleus and treatment of cells expressing survivin-GFP with the CK2 inhibitor TBB phenocopies this nuclear redistribution. Finally, we show T48 mutants have increased affinity for borealin, and that this association and cell proliferation can be restored by introduction of a second mutation at T97. To our knowledge these data are the first to identify T48 as a key regulatory site on survivin, and CK2 as a mediator of its mitotic and anti-apoptotic functions.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Motifs
  • Amino Acid Sequence
  • Apoptosis*
  • Casein Kinase II / metabolism
  • Casein Kinase II / physiology*
  • Cell Proliferation
  • Green Fluorescent Proteins / analysis
  • HeLa Cells
  • Humans
  • Inhibitor of Apoptosis Proteins / analysis
  • Inhibitor of Apoptosis Proteins / chemistry
  • Inhibitor of Apoptosis Proteins / physiology*
  • Mitosis*
  • Mutation
  • Phosphorylation
  • RNA Interference
  • Recombinant Fusion Proteins / analysis
  • Sequence Alignment
  • Sequence Analysis, Protein
  • Survivin
  • TNF-Related Apoptosis-Inducing Ligand
  • Threonine / chemistry

Substances

  • BIRC5 protein, human
  • Inhibitor of Apoptosis Proteins
  • Recombinant Fusion Proteins
  • Survivin
  • TNF-Related Apoptosis-Inducing Ligand
  • Green Fluorescent Proteins
  • Threonine
  • Casein Kinase II