Role of RNF20 in cancer development and progression - a comprehensive review.

Gautam Sethi,Alan Prem Kumar,Muthu K Shanmugam,Frank Arfuso

doi:10.1042/bsr20171287

Abstract

Evolving strategies to counter cancer initiation and progression rely on the identification of novel therapeutic targets that exploit the aberrant genetic changes driving oncogenesis. Several chromatin associated enzymes have been shown to influence post-translational modification (PTM) in DNA, histones, and non-histone proteins. Any deregulation of this core group of enzymes often leads to cancer development. Ubiquitylation of histone H2B in mammalian cells was identified over three decades ago. An exciting really interesting new gene (RING) family of E3 ubiquitin ligases, known as RNF20 and RNF40, monoubiquitinates histone H2A at K119 or H2B at K120, is known to function in transcriptional elongation, DNA double-strand break (DSB) repair processes, maintenance of chromatin differentiation, and exerting tumor suppressor activity. RNF20 is somatically altered in breast, lung, prostate cancer, clear cell renal cell carcinoma (ccRCC), and mixed lineage leukemia, and its reduced expression is a key factor in initiating genome instability; and it also functions as one of the significant driving factors of oncogenesis. Loss of RNF20/40 and H2B monoubiquitination (H2Bub1) is found in several cancers and is linked to an aggressive phenotype, and is also an indicator of poor prognosis. In this review, we summarized the current knowledge of RNF20 in chronic inflammation-driven cancers, DNA DSBs, and apoptosis, and its impact on chromatin structure beyond the single nucleosome level.

Highlights

Cancer is a disease that afflicts men and women, young and old, without any specific etiology
Recent advances in research and technology have identified additional inherent risk factors that may or may not be heritable, which range from cellular allelic mutations, somatic mutations, accumulating mutations such as hot spot mutation, homozygous gene deletion, or gene amplification, non-synonymous single nucleotide polymorphisms, inflammatory tumor microenvironment, angiogenesis, and epigenetic alterations in the genome of normal cells that transforms them into cancer cells with characteristic properties such as uncontrolled cell proliferation, and are associated with invasive and metastatic potential [1,2,3,4,5]
In a study by Zhang et al [63] (2011), USP22 was found to be up-regulated in breast cancer patient samples and was associated with aggressive phenotypes and decreased levels of ubiquitination of histone H2B (H2Bub1) compared with benign tumors

Summary

Introduction

Cancer is a disease that afflicts men and women, young and old, without any specific etiology. Ubiquitination of histone H2B (H2Bub1) has been demonstrated to be implicated in chromatin dynamics during transcription regulation, and previous studies have indicated that it is involved in homologous recombination by altering chromatin structure [20].

Results

Conclusion