Merck
  • Home
  • Search Results
  • E2 Ubiquitin-conjugating Enzyme, UBE2C Gene, Is Reciprocally Regulated by Wild-type and Gain-of-Function Mutant p53.

E2 Ubiquitin-conjugating Enzyme, UBE2C Gene, Is Reciprocally Regulated by Wild-type and Gain-of-Function Mutant p53.

The Journal of biological chemistry (2016-04-30)
Swati Bajaj, Sk Kayum Alam, Kumar Singha Roy, Arindam Datta, Somsubhra Nath, Susanta Roychoudhury
ABSTRACT

Spindle assembly checkpoint governs proper chromosomal segregation during mitosis to ensure genomic stability. At the cellular level, this event is tightly regulated by UBE2C, an E2 ubiquitin-conjugating enzyme that donates ubiquitin to the anaphase-promoting complex/cyclosome. This, in turn, facilitates anaphase-onset by ubiquitin-mediated degradation of mitotic substrates. UBE2C is an important marker of chromosomal instability and has been associated with malignant growth. However, the mechanism of its regulation is largely unexplored. In this study, we report that UBE2C is transcriptionally activated by the gain-of-function (GOF) mutant p53, although it is transcriptionally repressed by wild-type p53. We showed that wild-type p53-mediated inhibition of UBE2C is p21-E2F4-dependent and GOF mutant p53-mediated transactivation of UBE2C is NF-Y-dependent. We further explored that DNA damage-induced wild-type p53 leads to spindle assembly checkpoint arrest by repressing UBE2C, whereas mutant p53 causes premature anaphase exit by increasing UBE2C expression in the presence of 5-fluorouracil. Identification of UBE2C as a target of wild-type and GOF mutant p53 further highlights the contribution of p53 in regulation of spindle assembly checkpoint.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Anti-Goat IgG (whole molecule)–Peroxidase antibody produced in rabbit, affinity isolated antibody, buffered aqueous solution
Sigma-Aldrich
Anti-Mouse IgG (whole molecule)–Peroxidase antibody produced in rabbit, IgG fraction of antiserum, buffered aqueous solution
Sigma-Aldrich
Anti-Mouse Polyvalent Immunoglobulins (G,A,M)−Peroxidase antibody produced in goat, affinity isolated antibody
Sigma-Aldrich
Anti-Rabbit IgG (whole molecule)–Peroxidase antibody produced in goat, affinity isolated antibody
Sigma-Aldrich
Monoclonal Anti-β-Actin antibody produced in mouse, clone AC-74, purified immunoglobulin, buffered aqueous solution
Sigma-Aldrich
Z-Leu-Leu-Norvalinal, ≥90% (HPLC), powder
Sigma-Aldrich
IgG from rabbit serum, reagent grade, ≥95% (SDS-PAGE), essentially salt-free, lyophilized powder
Sigma-Aldrich
MISSION® esiRNA, targeting human TP53