A conserved serine residue regulates the stability of Drosophila Salvador and human WW domain-containing adaptor 45 through proteasomal degradation

Biochem Biophys Res Commun. 2013 Apr 19;433(4):538-41. doi: 10.1016/j.bbrc.2013.03.023. Epub 2013 Mar 21.

Abstract

The Hippo (Hpo) pathway is a conserved tumor suppressor pathway that controls organ size through the coordinated regulation of apoptosis and proliferation. Drosophila Salvador (Sav), which limits organ size, is a core component of the Hpo pathway. In this study, Ser-17 was shown to be important for the stability of Sav. Alanine mutation of Ser-17 promoted the proteasomal degradation of Sav. Destabilization and stabilization of the Sav protein mediated by alanine mutation of Ser-17 and by Hpo, respectively, were independent of each other. This implies that the stability of Sav is controlled by two mechanisms, one that is Ser-17-dependent and Hpo-independent, and another that is Ser-17-independent and Hpo-dependent. These dual mechanisms also regulated the human counterpart of Drosophila Sav, WW domain-containing adaptor 45 (WW45). The conservation of this regulation adds to its significance in normal physiology and tumorigenesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alanine / genetics
  • Alanine / metabolism
  • Animals
  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / metabolism*
  • Cell Line, Tumor
  • Drosophila / genetics
  • Drosophila / metabolism*
  • Drosophila Proteins / genetics
  • Drosophila Proteins / metabolism*
  • Electrophoresis, Polyacrylamide Gel
  • Humans
  • Intracellular Signaling Peptides and Proteins / genetics
  • Intracellular Signaling Peptides and Proteins / metabolism
  • Leupeptins / pharmacology
  • Mutagenesis, Site-Directed
  • Mutation
  • Proteasome Endopeptidase Complex / drug effects
  • Proteasome Endopeptidase Complex / metabolism*
  • Protein Serine-Threonine Kinases / genetics
  • Protein Serine-Threonine Kinases / metabolism
  • Protein Stability
  • Proteolysis
  • Serine / genetics
  • Serine / metabolism*
  • Species Specificity
  • Transfection

Substances

  • Cell Cycle Proteins
  • Drosophila Proteins
  • Intracellular Signaling Peptides and Proteins
  • Leupeptins
  • SAV1 protein, human
  • sav protein, Drosophila
  • Serine
  • Protein Serine-Threonine Kinases
  • hpo protein, Drosophila
  • Proteasome Endopeptidase Complex
  • Alanine
  • benzyloxycarbonylleucyl-leucyl-leucine aldehyde