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Diverse roles of the E2/E3 hybrid enzyme UBE 2O in the regulation of protein ubiquitination, cellular functions, and disease onset
Author(s) -
Ullah Kifayat,
Zubia Emmanuel,
Narayan Mahesh,
Yang Jing,
Xu Guoqiang
Publication year - 2019
Publication title -
the febs journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 204
eISSN - 1742-4658
pISSN - 1742-464X
DOI - 10.1111/febs.14708
Subject(s) - ubiquitin , ubiquitin conjugating enzyme , ubiquitin ligase , biology , deubiquitinating enzyme , proteostasis , proteasome , ubiquitin protein ligases , biochemistry , microbiology and biotechnology , gene
The ubiquitin‐proteasome system is an important regulatory machinery involved in proteostasis and cellular signaling. Proteins are ubiquitinated via the concerted action of E1 ubiquitin‐activating enzymes, E2 ubiquitin‐conjugating enzymes, and E3 ubiquitin ligases. Although most of the studies to date focus on the significance of E3 ubiquitin ligases in disease development and therapeutic treatment, recent discoveries suggest that E2 ubiquitin‐conjugating enzymes might also be potential drug targets. The ubiquitin‐conjugating enzyme E2 O ( UBE 2O), an E3‐independent E2 (i.e. an E2/E3 hybrid enzyme), can directly mediate the ubiquitination of many substrates. These include 5′‐ AMP ‐activated protein kinase catalytic subunit α2 ( AMPK α2), tumor suppressor ubiquitin carboxyl‐terminal hydrolase BAP 1, mixed‐lineage leukemia ( MLL ) protein, SMAD family member 6 ( SMAD 6), transcription factor c‐Maf and aryl hydrocarbon receptor nuclear translocator‐like protein 1 ( ARNTL or BMAL 1), and free ribosomal proteins, which are ubiquitinated in distinct ways, thereby associating UBE 2O with a variety of biological functions. Furthermore, UBE 2O is frequently amplified or mutated in multiple cancers, and its high expression is associated with low survival rate of gastric, lung, breast, and prostate cancer patients. However, the molecular mechanisms by which UBE 2O contributes to tumor initiation and progression are not fully elucidated. This review focuses on emerging insights from genetics, biochemistry, and cell biology to explore the biological functions of UBE 2O and its therapeutic potential.