Structure and function of the co-chaperone protein phosphatase 5 in cancer

Cell Stress Chaperones. 2020 May;25(3):383-394. doi: 10.1007/s12192-020-01091-3. Epub 2020 Apr 2.

Abstract

Protein phosphatase 5 (PP5) is a serine/threonine protein phosphatase that regulates many cellular functions including steroid hormone signaling, stress response, proliferation, apoptosis, and DNA repair. PP5 is also a co-chaperone of the heat shock protein 90 molecular chaperone machinery that assists in regulation of cellular signaling pathways essential for cell survival and growth. PP5 plays a significant role in survival and propagation of multiple cancers, which makes it a promising target for cancer therapy. Though there are several naturally occurring PP5 inhibitors, none is specific for PP5. Here, we review the roles of PP5 in cancer progression and survival and discuss the unique features of the PP5 structure that differentiate it from other phosphoprotein phosphatase (PPP) family members and make it an attractive therapeutic target.

Keywords: Cancer; Clear cell renal cell carcinoma; Co-chaperone; Heat shock protein 90; Molecular chaperone; Post-translational modifications; Serine/threonine phosphatase 5.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Breast Neoplasms / enzymology
  • Catalytic Domain
  • Female
  • HSP90 Heat-Shock Proteins / metabolism
  • Humans
  • Neoplasms / drug therapy
  • Neoplasms / enzymology*
  • Nuclear Proteins / antagonists & inhibitors
  • Nuclear Proteins / chemistry*
  • Nuclear Proteins / metabolism
  • Nuclear Proteins / physiology*
  • Phosphoprotein Phosphatases / antagonists & inhibitors
  • Phosphoprotein Phosphatases / chemistry*
  • Phosphoprotein Phosphatases / metabolism
  • Phosphoprotein Phosphatases / physiology*

Substances

  • HSP90 Heat-Shock Proteins
  • Nuclear Proteins
  • Phosphoprotein Phosphatases
  • protein phosphatase 5