Sehbanul Islam

Conference 2022 Pre-recorded Presentation

 

Video title

β -Trcp1 and β -Trcp2 Cross-Regulation Controls the DNA Damage Response and Breast Cancer Tumorigenesis

 

Authors and Affiliations

Sehbanul Islam1,2 and Manas Kumar Santra2

1. Department of Cancer Biology, University of Pennsylvania 2. Molecular Oncology Laboratory, National Centre for Cell Science, Pune, Maharashtra, India

 

Abstract

Background

β-TrCP, an F-box protein has two paralogs β-TrCP1 and β-TrCP2. Several studies suggested that these proteins are redundant in function and regulate several cell cycle and survival factors influencing tumor growth and survival. However, few recent reports indicate their differential role which needs further investigation.

Methods

In this study, we used biochemical, molecular biology, flow cytometric, and immunofluorescence techniques.

Results

Here, we demonstrate that β-TrCP1 and β-TrCP2 show distinct function in DNA damage response and breast cancer tumorigenesis. β-TrCP1 and β-TrCP2 regulates each other through polyubiquitination mediated proteasomal degradation. β-TrCP1 inhibits cell proliferation, growth, and migration of breast cancer cells whereas β-TrCP2 shows opposite effect. These results suggest that the β-TrCP1 acts as a tumor suppressor gene and β-TrCP2 acts as an oncogene, supporting different roles for the two paralogs in tumor development. Moreover, results demonstrated that β-TrCP1 levels are induced while β-TRCP2 levels are declined upon DNA damage. β-TrCP1 promotes polyubiquitination mediated degradation of β-TrCP2 upon DNA damage to stabilize p53 for cell cycle arrest.

Conclusions

In this study, we examined the direct cross-regulation of β-TrCP1 and β-TrCP2 proteins and found that β-TrCP2 could interfere with the tumor suppressive function of β-TrCP1 during cancer progression while β-TrCP1 maintains β-TrCP2 level in response to DNA damage.