Ubiquitin- and ubiquitin-like proteins-conjugating enzymes (E2s) in breast cancer

Abstract

Breast cancer is the most common malignancy in women and a significant cause of morbidity and mortality. Sub-types of breast cancer defined by the expression of steroid hormones and Her2/Neu oncogene have distinct prognosis and undergo different therapies. Besides differing in their phenotype, sub-types of breast cancer display various molecular lesions that participate in their pathogenesis. BRCA1 is one of the common hereditary cancer predisposition genes and encodes for an ubiquitin ligase. Ubiquitin ligases or E3 enzymes participate together with ubiquitin activating enzyme and ubiquitin conjugating enzymes in the attachment of ubiquitin (ubiquitination) in target proteins. Ubiquitination is a post-translational modification regulating multiple cell functions. It also plays important roles in carcinogenesis in general and in breast carcinogenesis in particular. Ubiquitin conjugating enzymes are a central component of the ubiquitination machinery and are often perturbed in breast cancer. This paper will discuss ubiquitin and ubiquitin-like proteins conjugating enzymes participating in breast cancer pathogenesis, their relationships with other proteins of the ubiquitination machinery and their role in phenotype of breast cancer sub-types.

Long noncoding RNA MEG3 regulates LATS2 by promoting the ubiquitination of EZH2 and inhibits proliferation and invasion in gallbladder cancer

“…Ubiquitination is a significant post-translational modification process in which the modified proteins are attached to the Ub, and their stability and functions in multiple cell processes and diseases, especially cancer development, are regulated 19 , 20 . Wu and Zhang 21 found that the phosphorylation of EZH2 at the Thr-345 and Thr-487 sites promoted the ubiquitination of EZH2 and subsequent degradation by the ubiquitin–proteasome pathway.…”

Roles of Ubiquitination and SUMOylation on Prostate Cancer: Mechanisms and Clinical Implications

“…The E2 enzyme UBE2B, increases the polyubiquitination of β-Catenin, a protein that is frequently upregulated in cancer cells [ 24 ]. In addition, UBE2B cooperates with MDM2, an E3 Ub ligase, in a complex to assist the ubiquitination and degradation of the p53 tumor suppressor [ 25 ].…”

E2 superfamily of ubiquitin-conjugating enzymes: constitutively active or activated through phosphorylation in the catalytic cleft

“…This catalytic core domain is known as the Ub iquitin C onjugation (UBC) domain and contains the catalytic cysteine, which forms a thioester bond with Ub 45 46 47 . E2s recently gained attention as targets to design inhibitory molecules 49 50 51 52 53 since their aberrant regulation is associated with cancer or neurodegenerative diseases 54 55 56 .…”