Case Report

Biomedical Research and Therapy

, 1:22

First online:

Open Access This content is freely available online to anyone, anywhere at any time.

Constitutive Photomorphogensis Protein1 (COP1) mediated p53 pathway and its oncogenic role

  • Md. Golam RabbaniAffiliated withBiotechnology and Genetic Engineering Discipline, Khulna University
  • , Sk. Amir HossainAffiliated withBiotechnology and Genetic Engineering Discipline, Khulna UniversityDepartment of Biological Sciences, King Abdulaziz University Email author 
  • , Khandker Khaldun IslamAffiliated withBiotechnology and Genetic Engineering Discipline, Khulna University
  • , Sarder Nasir UddinAffiliated withBiotechnology and Genetic Engineering Discipline, Khulna University

Abstract

We have reviewed the COP1 mediated tumor suppressor protein p53 pathway and its oncogenic role. COP1 is a negative regulator of p53 and acts as a pivotal controller of p53-Akt death-live switch (Protein kinase B). In presence of p53, COP1 is overexpressed in breast, ovarian, gastric cancers, even without MDM2 (Mouse double minute-2) amplification. Following DNA damage, COP1 is phosphorylated instantly by ATM (Ataxia telangiectasia mutated) and degraded by 14-3-3σ following nuclear export and enhancing ubiquitination. In ATM lacking cell, other kinases, i.e. ATR (ataxia telangiectasia and Rad3-related protein), Jun kinases and DNA-PK (DNA-dependent protein kinase) cause COP1 & CSN3 (COP9 signalosome complex subunit-3) phosphorylation and initiate COP1’s down regulation. Although, it has been previously found that co-knockout of MDM2 and COP1 enhance p53’s half-life by eight fold, the reason is still unknown. Additionally, while interacting with p53, COP1 upregulate MDM2’s E3 ubiquitin ligase, Akt, CSN6 (COP9 signalosome 6) activity and inhibit 14-3-3σ’s negative regulation on MDM2 and COP1 itself. Conclusively, there persists an amplification loop among COP1, MDM2, Akt and 14-3-3σ to regulate p53’s stability and activity. However, the role of another tumor suppressor PTEN (phosphatase and tensin homologue) is yet to be discovered. This study provides insight on the molecular genetic pathways related to cancer and might be helpful for therapeutic inventions.

Keywords

COP1 p53 14-3-3σ PTEN MDM2 ATM Akt CSN3 CSN6 MLF1