Parkin: A targetable linchpin in human malignancies

Biochim Biophys Acta Rev Cancer. 2021 Aug;1876(1):188533. doi: 10.1016/j.bbcan.2021.188533. Epub 2021 Mar 27.

Abstract

Parkin, an E3 ubiquitin ligase has been found to be deregulated in a variety of human cancers. Our current understanding is endowed with strong evidences that Parkin plays crucial role in the pathogenesis of cancer by controlling/interfering with major hallmarks of cancer delineated till today. Consistent with the idea of mitophagy, the existing studies imitates the tumor suppressive potential of Parkin, resolved by its capacity to regulate cell proliferation, cell migration, angiogenesis, apoptosis and overall cellular survival. Dysfunction of Parkin has resulted in the loss of ubiquitination of cell cycle components followed by their accumulation leading to genomic instability, perturbed cell cycle and eventually tumor progression. In this review, we provide an overview of current knowledge about the critical role of Parkin in cancer development and progression and have focussed on its therapeutic implications highlighting the diagnostic and prognostic value of Parkin as a biomarker. We earnestly hope that an in-depth knowledge of Parkin will provide a linchpin to target in various cancers that will open a new door of clinical applications and therapeutics.

Keywords: Biomarker; Cancer; E3 ubiquitin ligase; Parkin (PARK2/PRKN); Therapeutics; Tumor suppressor gene.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Antineoplastic Agents / therapeutic use
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism
  • Enzyme Activation
  • Enzyme Activators / therapeutic use
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Molecular Targeted Therapy
  • Neoplasms / drug therapy
  • Neoplasms / enzymology*
  • Neoplasms / genetics
  • Neoplasms / pathology
  • Signal Transduction
  • Ubiquitin-Protein Ligases / genetics
  • Ubiquitin-Protein Ligases / metabolism*

Substances

  • Antineoplastic Agents
  • Biomarkers, Tumor
  • Enzyme Activators
  • Ubiquitin-Protein Ligases
  • parkin protein