Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
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Query: UMLS:C0033036 (
APC
)
10,214
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Evasion of apoptosis allows many cancers to resist chemotherapy. Apoptosis is mediated by the serial activation of caspase family proteins. These proteases are often activated upon the release of cytochrome c from the mitochondria, which is promoted by the proapoptotic Bcl-2 family protein, Bax. This function of Bax is enhanced by the MOAP-1 (modulator of apoptosis protein 1) protein in response to DNA damage. Previously, we reported that MOAP-1 is targeted for ubiquitylation and degradation by the
APC
/C
Cdh1
ubiquitin ligase. In this study, we identify the HECT (homologous to the E6-AP carboxyl terminus) family E3 ubiquitin ligase,
UBR5
, as a novel ubiquitin ligase for MOAP-1. We demonstrate that
UBR5
interacts physically with MOAP-1, ubiquitylates MOAP-1 in vitro and inhibits MOAP-1 stability in cultured cells. In addition, we show that Dyrk2 kinase, a reported
UBR5
interactor, cooperates with
UBR5
in mediating MOAP-1 ubiquitylation. Importantly, we found that cisplatin-resistant ovarian cancer cell lines exhibit lower levels of MOAP-1 accumulation than their sensitive counterparts upon cisplatin treatment, consistent with the previously reported role of MOAP-1 in modulating cisplatin-induced apoptosis. Accordingly,
UBR5
knockdown increased MOAP-1 expression, enhanced Bax activation and sensitized otherwise resistant cells to cisplatin-induced apoptosis. Furthermore,
UBR5
expression was higher in ovarian cancers from cisplatin-resistant patients than from cisplatin-responsive patients. These results show that
UBR5
downregulates proapoptotic MOAP-1 and suggest that
UBR5
can confer cisplatin resistance in ovarian cancer. Thus
UBR5
may be an attractive therapeutic target for ovarian cancer treatment.
...
PMID:Downregulation of the proapoptotic protein MOAP-1 by the UBR5 ubiquitin ligase and its role in ovarian cancer resistance to cisplatin. 2960 95
Mucosal melanoma is a rare malignant melanoma with more aggressive and poorer outcomes. The incidence of mucosal melanoma varies greatly among different ethnic groups. We herein sought to characterize the vital genes and pathways of Chinese mucosal melanoma patients. By whole-exome sequencing in six patients with mucosal melanoma, we detected a total of 21,733 CNVs and 2372 SNPs. The CNV/SNP burden varies greatly between individuals, including recurrent CNV targeting PIK3 family, KRAS,
APC
and BRCA1. Significantly mutated genes were NUDT5, ZBTB18, NEURL4, ZNF430, RBM44, GAK, PCDHA13, STK38 and
UBR5
. Besides, FAT1 gene was identified frequently mutated in anorectal melanoma patients (3/3, 100%). Moreover, our result showed that HPV infection may be associated with mucosal melanoma. In conclusion, this study indicated that mucosal melanomas have a low SNPs burden and a high number of CNVs and expand the spectrum of mucosal melanoma variants, also provided an insight for the pathological mechanism of mucosal melanoma.
...
PMID:Identification of vital genes and pathways associated with mucosal melanoma in Chinese. 3318 33
