Regulation of the retinoblastoma-E2F pathway by the ubiquitin-proteasome system

Biochimica Et Biophysica Acta
Satyaki Sengupta, R William Henry

Abstract

The retinoblastoma tumor suppressor (RB) and its related family members p107 and p130 regulate cell proliferation through the transcriptional repression of genes involved in cellular G1 to S phase transition. However, RB proteins are functionally versatile, and numerous genetic and biochemical studies point to expansive roles in cellular growth control, pluripotency, and apoptotic response. For the vast majority of genes, RB family members target the E2F family of transcriptional activators as an integral component of its gene regulatory mechanism. These interactions are regulated via reversible phosphorylation by Cyclin/Cyclin-dependent kinase (Cdk) complexes, a major molecular mechanism that regulates transcriptional output of RB/E2F target genes. Recent studies indicate an additional level of regulation involving the ubiquitin-proteasome system that renders pervasive control over each component of the RB pathway. Disruption of the genetic circuitry for proteasome-mediated targeting of the RB pathway has serious consequences on development and cellular transformation, and is associated with several forms of human cancer. In this review, we discuss the role of the ubiquitin-proteasome system in proteolytic control of RB-E2F pa...Continue Reading

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Citations

Mar 22, 2016·Biomarkers in Cancer·Kazushi Inoue, Elizabeth A Fry
Apr 6, 2019·Combinatorial Chemistry & High Throughput Screening·Jiangshan LianYida Yang
Feb 28, 2020·Annals of Clinical and Translational Neurology·Theresa BrunetMatias Wagner
Jan 5, 2017·Genes & Cancer·Jesús Hernández-MongeVanesa Olivares-Illana
Mar 9, 2017·Cancer Biomarkers : Section a of Disease Markers·Hala Abdel Al Ahmed, Ola Nada
Jan 21, 2017·Endocrine-related Cancer·Maria Santa RoccaAlberto Ferlin
Jul 27, 2018·Evidence-based Complementary and Alternative Medicine : ECAM·Eun Sik ChoiHo Sub Lee
Jul 25, 2019·Frontiers in Endocrinology·Luca De ToniAndrea Garolla
Jul 19, 2017·Trends in Cancer·Satyaki Sengupta, Rani E George
Sep 10, 2020·Molecular Pharmaceutics·Prabhjeet SinghDeepak Chitkara

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