Cdk5 links with DNA damage response and cancer

Mol Cancer. 2017 Mar 14;16(1):60. doi: 10.1186/s12943-017-0611-1.

Abstract

As an atypical member of cyclin dependent kinase family, Cyclin dependent kinase 5 (Cdk5) is considered as a neuron-specific kinase in the past decade due to the abundant existence of its activator p35 in post-mitotic neurons. Recent studies show that Cdk5 participates in a series of biological and pathological processes in non-neuronal cells, and is generally dysregulated in various cancer cells. The inhibition or knockdown of Cdk5 has been proven to play an anti-cancer role through various mechanisms, and can synergize the killing effect of chemotherapeutics. DNA damage response (DDR) is a series of regulatory events including DNA damage, cell-cycle arrest, regulation of DNA replication, and repair or bypass of DNA damage to ensure the maintenance of genomic stability and cell viability. Here we describe the regulatory mechanisms of Cdk5, its controversial roles in apoptosis and focus on its links to DDR and cancer.

Keywords: Apoptosis; Cancer; Cyclin dependent kinase 5; DNA damage response; Targeted cancer therapy.

Publication types

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

MeSH terms

  • Animals
  • Apoptosis
  • Cell Cycle Checkpoints
  • Cyclin-Dependent Kinase 5 / antagonists & inhibitors
  • Cyclin-Dependent Kinase 5 / genetics
  • Cyclin-Dependent Kinase 5 / metabolism*
  • DNA Damage*
  • DNA Replication
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Molecular Targeted Therapy
  • Neoplasms / drug therapy
  • Neoplasms / genetics*
  • Neoplasms / metabolism*
  • Neoplasms / pathology
  • Protein Binding
  • Signal Transduction / drug effects

Substances

  • Cyclin-Dependent Kinase 5