Ubiquitin-Conjugating Enzyme UBE2Q2 Suppresses Cell Proliferation and Is Down-Regulated in Recurrent Head and Neck Cancer

Abstract

The ubiquitin-proteasome system has a crucial role in maintaining and regulating cellular homeostasis including carcinogenesis. UBE2Q2, also designated Ubci, is one of the ubiquitin-conjugating enzymes (E2), and it has been reported that mRNA of UBE2Q2 is highly expressed in human head and neck squamous cell carcinoma, particularly hypopharyngeal carcinoma. However, the involvement of UBE2Q2 in carcinogenesis has not been fully elucidated. Most cases of head and neck carcinoma are treated with cis-diamminedichloroplatinum (II; CDDP) or docetaxel, which are the most effective chemotherapeutic agents against squamous cell carcinomas. Nevertheless, some head and neck cancers develop resistance to these drugs, although the causes and mechanisms remain unknown. In this study, we found high expression levels of UBE2Q2 in human head and neck carcinoma cell lines and cancer tissues by using an anti-UBE2Q2 antibody at the protein level. We also found that the expression level of UBE2Q2 is decreased in cell lines and cancer tissues that have resistance to CDDP or docetaxel and in cancer tissues treated with CDDP or docetaxel. Furthermore, we found that overexpression of UBE2Q2 affects cell proliferation and anchorage-independent cell growth. These findings suggest that UBE2Q2 is a novel oncosuppressor that inhibits tumor growth and is related to the resistance to anticarcinoma agents and that UBE2Q2 likely functions as a novel diagnostic tool and a potentially therapeutic target for head and neck squamous cell carcinoma. (Mol Cancer Res 2009;7(9):1553-62)

A Complex Regulatory Network Coordinating Cell Cycles DuringC. elegansDevelopment Is Revealed by a Genome-Wide RNAi Screen

“…Similarly, a significant increase in the expression of a murine ortholog, UBE2Q1, was observed during B-cell development at a stage when proliferation is abruptly terminated (Seita et al 2012). These observations correlating UBE2Q2 expression with differentiation and inhibition of proliferation are consistent with the accumulation of cells in the G 0 and G 1 phases upon experimental UBE2Q2 overexpression (Maeda et al 2009; Seghatoleslam et al 2012). Thus, it remains to be determined whether the mammalian UBE2Q2 acts similar to UBC-25 in physiologic cell-cycle quiescence.…”

“…Accordingly, ubc-25 was examined as an example of a potentially fundamental regulator of cell-cycle quiescence during metazoan development. UBC-25 exhibited high amino acid sequence conservation with UBE2Q2, a metazoan specific UBC implicated in cancer (Schulze et al 2003; Melner et al 2006; Maeda et al 2009). Although we identified C. elegans ubc-25 as a regulator of VPC cell-cycle quiescence, an analyses of VPC number at the L2-to-L3 molt indicated that extra cell divisions were rare in the ubc-25 loss-of-function animals (Table 1).…”

“…UBE2Q2 was independently identified as a potential mitotic regulator (Banerjee et al 2007), a gene expressed by the luminal epithelium of the endometrium at the embryo implantation site (UBCi; Melner et al 2006), and as a gene overexpressed in head and neck tumors (LOC92912; Seghatoleslam et al 2006). The observations that cancers of several cell origins overexpress UBE2Q2 at both the transcript and protein levels (Seghatoleslam et al 2006; Maeda et al 2009; Nikseresht et al 2010) suggested a role in promoting proliferation and/or transformation. However, it is possible that the observed overexpression is actually the indirect result of a malfunctioning feedback system.…”

Ubiquitin-like protein conjugation and the ubiquitin–proteasome system as drug targets

“…Several studies have linked E2s from different ubiquitin-like protein (UBL) pathways to cancer and other diseases, including UBE2Q2 in head and neck squamous cell carcinoma 119 ; the SUMO E2 UBC9 in ovarian carcinoma, melanoma, lung adenocarcinoma and breast cancer [120][121][122] ; UBE2T in lung cancer 123 ; and UBCH10 in chromosomal instability and tumour formation 124,125 . In all cases, an E2 must engage its respective E1 to be charged with a UBL through transthiolation.…”

UBE2Q1 expression in human colorectal tumors and cell lines

“…In vivo inhibition of this protein is also shown to result in early mitotic arrest and cytotoxicity in cells treated with microtubule-inhibiting agents. 18 , 19 …”