Bioinformatics and Systems Medicine Laboratory
General information | Expression | Regulation | Mutation | Interaction

Basic Information

Gene ID

115426

Name

UHRF2

Synonymous

NIRF|RNF107|URF2;ubiquitin-like with PHD and ring finger domains 2;UHRF2;ubiquitin-like with PHD and ring finger domains 2

Definition

E3 ubiquitin-protein ligase UHRF2|Np95-like ring finger protein|RING finger protein 107|np95/ICBP90-like RING finger protein|nuclear protein 97|nuclear zinc finger protein NP97|ubiquitin-like PHD and RING finger domain-containing protein 2|ubiquitin-like,

Position

9p24.1

Gene type

protein-coding

Source

Count: 1; Pubmed_search

Sentence

Abstract

NIRF constitutes a nodal point in the cell cycle network and is a candidate tumor suppressor.

In biological networks, a small number of "hub" proteins play critical roles in the network integrity and functions. The cell cycle network orchestrates versatile cellular functions through interactions between many signaling modules, whose defects impair diverse cellular processes, often leading to cancer. However, the network architecture and molecular basis that ensure proper coordination between distinct modules are unclear. Here, we show that the ubiquitin ligase NIRF (also known as UHRF2), which induces G1 arrest, interacts with multiple cell cycle proteins including cyclins (A2, B1, D1 and E1), p53 and pRB, and ubiquitinates cyclins D1 and E1. Consistent with its versatility, a bioinformatic network analysis demonstrated that NIRF is an intermodular hub protein that is responsible for the coordination of multiple network modules. Notably, intermodular hubs are frequently associated with oncogenesis. Indeed, we detected loss of heterozygosity of the NIRF gene in several kinds of tumors. When a cancer outlier profile analysis was applied to the Oncomine database, loss of the NIRF gene was found at statistically significant levels in diverse tumors. Importantly, a recurrent microdeletion targeting NIRF was observed in non-small cell lung carcinoma. Furthermore, NIRF is immediately adjacent to the single nucleotide polymorphism rs719725, which is reportedly associated with the risk of colorectal cancer. These observations suggest that NIRF occupies a prominent position within the cell cycle network, and is a strong candidate for a tumor suppressor whose aberration contributes to the pathogenesis of diverse malignancies.CI - (c) 2011 Landes Bioscience

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