Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P43146 (tumour suppressor)
 5,935 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The p53 tumour suppressor protein can be rendered ineffective by mutations in the p53 gene or by interactions with proteins of DNA-transforming viruses, including Human Papillomaviruses (HPVs). Our aim was to determine whether the inactivation of p53, caused by a mutation of gene itself or by HPV is involved in anogenital carcinogenesis. We studied p53 overexpression by immunohistochemical methods, and HPV/DNA by non isotopic in situ hybridization method in 137 anogenital lesions. Immunoreactivity for p53 was seen in 5% of condylomata acuminata, in 12% of low-grade CINs, in 3.5% of high-grade CINs, and in 17% of invasive cervical carcinomas. Two (67%) of three condylomata acuminate p53+ harboured HPV/DNA. The concomitant presence of p53 and HPV was not detected in intraepithelial and invasive cervical lesions. Our findings suggest that p53 inactivation does not seem to play an important role in anogenital carcinogenesis. Further investigation of the concomitant presence of p53 and HPV in condylomata acuminate and its role in recurrences or progression of these lesions is needed.
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PMID:Immunohistochemical detection of p53 protein in anogenital lesions and its relationship with HPV status. 989 51

Human papillomaviruses (HPVs) are aetiological agents for genital warts and cervical cancer, the different pathologies of which are dependent on the type of HPV infection. Oncogenic HPV types associated with cancer are carcinogens by virtue of their oncogene products, which target key regulators of cell proliferation and apoptosis. The viral E6 protein from oncogenic HPV types plays a central role in carcinogenesis by exploiting the cellular proteasome degradation pathway in order to mediate the degradation of cellular proteins, most notably the prototype tumour suppressor protein p53. Much less is known about the cellular targets of E6 from the non-oncogenic HPV types associated with genital warts. It is also unclear what factors influence the level and stability of the viral E6 proteins in cells. This report demonstrates that both oncogenic and non-oncogenic HPV E6 proteins (from types 18 and 11, respectively) are ubiquitinated and targeted for degradation by the 26S proteasome. E6 domains required for the induction of p53 or DLG degradation, or E6AP binding, are not involved in proteasome-mediated degradation of HPV-18 E6. These results provide insight into the cellular modulation of E6 protein levels from both high-risk and low-risk HPV types.
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PMID:Ubiquitination and proteasome degradation of the E6 proteins of human papillomavirus types 11 and 18. 1516 24