HSP60 overexpression increases the protein levels of the p110α subunit of phosphoinositide 3-kinase and c-Myc

Clin Exp Pharmacol Physiol. 2015 Oct;42(10):1092-7. doi: 10.1111/1440-1681.12457.

Abstract

Heat shock protein 60 (HSP60) is a chaperone protein which plays an essential role in facilitating the folding of many newly synthesized proteins to reach their native forms. Increased HSP60 expression is observed in various types of human cancers. However, proteins induced by HSP60 to mediate transformation remain largely unknown. Here we show that HSP60 overexpression increases the protein levels of the p110α subunit of phosphoinositide 3-kinase (PI3K). The amino acid domain 288-383 of HSP60 is used to increase the protein levels. Overexpression of HSP60 also induces the levels of phosphorylated Akt. In addition, the amino acid domain 288-383 of HSP60 is used to induce c-Myc expression. Finally, a mono-ubiquitinated form of β-catenin has a higher activity to activate β-catenin downstream targets compared to wild-type β-catenin. These results indicate that HSP60 overexpression induces the levels or activity of multiple oncogenic proteins to mediate transformation.

Keywords: Heat shock protein 60 (HSP60); c-Myc; p110α; transformation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Chaperonin 60 / genetics*
  • Class III Phosphatidylinositol 3-Kinases / chemistry
  • Class III Phosphatidylinositol 3-Kinases / metabolism*
  • Enzyme Activation
  • Gene Expression
  • HEK293 Cells
  • Humans
  • Protein Structure, Tertiary
  • Proto-Oncogene Proteins c-akt / metabolism
  • Proto-Oncogene Proteins c-myc / chemistry
  • Proto-Oncogene Proteins c-myc / metabolism*
  • beta Catenin / metabolism

Substances

  • Chaperonin 60
  • Proto-Oncogene Proteins c-myc
  • beta Catenin
  • Class III Phosphatidylinositol 3-Kinases
  • Proto-Oncogene Proteins c-akt