Phosphorylation: Implications in Cancer

Protein J. 2017 Feb;36(1):1-6. doi: 10.1007/s10930-017-9696-z.

Abstract

Post translational modifications (PTMs) are involved in variety of cellular activities and phosphorylation is one of the most extensively studied PTM, which regulates a number of cellular functions like cell growth, differentiation, apoptosis and cell signaling in healthy condition. However, alterations in phosphorylation pathways result in serious outcomes in the form of diseases, especially cancer. Many signalling pathways including Tyrosine kinase, MAP kinase, Cadherin-catenin complex, Cyclin-dependent kinase etc. are major players of the cell cycle and deregulation in their phosphorylation-dephosphorylation cascade has been shown to be manifested in the form of various types of cancers. Tyrosine kinase family encompasses the greatest number of oncoproteins. MAPK cascade has an importance role in cancer growth and progression. Bcl-2 family proteins serve either proapoptotic or antiapoptotic function. Cadherin-catenin complex regulates cell adhesion properties and cyclins are the key regulators of cell cycle. Altered phosphorylations in any of the above pathways are strongly associated with cancer, at the same time they serve as the potential tergets for drug development against cancer. Drugs targeting tyrosine kinase are potent anticancer drugs. Inhibitors of MEK, PI3K and ERK signalling pathways are undergoing clinical trials. Thus, drugs targeting phosphorylation pathways represent a promising area for cancer therapy.

Keywords: Cadherins; Cyclins; Mitogen-activated protein kinase; Nuclear factor-κB; Phosphorylation; Tyrosine kinase.

Publication types

  • Review

MeSH terms

  • Animals
  • MAP Kinase Signaling System*
  • Neoplasm Proteins / antagonists & inhibitors
  • Neoplasm Proteins / chemistry
  • Neoplasm Proteins / genetics
  • Neoplasm Proteins / metabolism*
  • Neoplasms / drug therapy
  • Neoplasms / genetics
  • Neoplasms / metabolism*
  • Neoplasms / pathology
  • Phosphorylation / drug effects
  • Phosphorylation / genetics
  • Protein Kinase Inhibitors / therapeutic use

Substances

  • Neoplasm Proteins
  • Protein Kinase Inhibitors