The p53 tumor suppressor protein is a principal mediator of growth arrest, senescence, and apoptosis inresponse to a broad array of cellular damage. p53 is a substrate for the ubiquitin-proteasome system, however,the ubiquitin-conjugating enzymes (E2s) involved in p53 ubiquitination have not been well studied. UBE2Q1 isa novel E2 ubiquitin conjugating enzyme gene. Here, we investigated the effect of UBE2Q1 overexpression onthe level of p53 in the MDA-MB-468 breast cancer cell line as well as the interaction between UBE2Q1 and p53.By using a lipofection method, the p53 mutated breast cancer cell line, MDA-MB-468, was transfected withthe vector pCMV6-AN-GFP, containing UBE2Q1 ORF. Western blot analysis was employed to verify theoverexpression of UBE2Q1 in MDA-MB-468 cells and to evaluate the expression level of p53 before and aftercell transfection. Immunoprecipitation and GST pull-down protocols were used to investigate the binding ofUBE2Q1 to p53. We established MDA-MB-468 cells that transiently expressed a GFP fusion proteins containingUBE2Q1 (GFP-UBE2Q1). Western blot analysis revealed that levels of p53 were markedly lower in UBE2Q1transfected MDA-MB-468 cells as compared with control MDA-MB-468 cells. Both in vivo and in vitro datashowed that UBE2Q1 co-precipitated with p53 protein. Our data for the first time showed that overexpressionof UBE2Q1can lead to the repression of p53 in MDA-MB-468 cells. This repression of p53 may be due to itsUBE2Q1 mediated ubiquitination and subsequent proteasome degradation, a process that may involve directinteraction of UBE2Q1with p53.