Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0019163 (hepatitis B)
 38,309 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cyclophilins (Cyps), the intracellular receptor for immunosuppressant cyclosporine A (CsA), play important cellular roles through activities of peptidyl-prolyl cis-trans isomerase (PPIase) and chaperones. Cyps are structurally conserved and found in both prokaryotic and eukaryotic organisms, including humans which contain 16 Cyp isoforms. Although human Cyps were identified about 25 years ago, their physiological and pathological roles have only been the focus of attention recently because of their possible involvement in diseases and ailments such as HIV infection, hepatitis B and C viral infection, atherosclerosis, ER stress-related diseases and neurodegenerative diseases, etc. There are reports for upregulated Cyps in many human cancers and there are also strong correlations found between Cyps overexpression and malignant transformation. This review discusses the important and diverse roles of Cyps overexpression in human cancers. Understanding biological functions of Cyps will eventually lead to improved strategies for cancer treatment and prevention.
 ...
PMID:Current implications of cyclophilins in human cancers. 2063 27

TP53 missense mutations significantly influence the development and progression of various human cancers via their gain of new functions (GOF) through different mechanisms. Here we report a unique mechanism underlying the GOF of p53-R249S (p53-RS), a p53 mutant frequently detected in human hepatocellular carcinoma (HCC) that is highly related to hepatitis B infection and aflatoxin B1. A CDK inhibitor blocks p53-RS's nuclear translocation in HCC, whereas CDK4 interacts with p53-RS in the G1/S phase of the cells, phosphorylates it, and enhances its nuclear localization. This is coupled with binding of a peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (PIN1) to p53-RS, but not the p53 form with mutations of four serines/threonines previously shown to be crucial for PIN1 binding. As a result, p53-RS interacts with c-Myc and enhances c-Myc-dependent rDNA transcription key for ribosomal biogenesis. These results unveil a CDK4-PIN1-p53-RS-c-Myc pathway as a novel mechanism for the GOF of p53-RS in HCC.
 ...
PMID:Mutant p53 Gains Its Function via c-Myc Activation upon CDK4 Phosphorylation at Serine 249 and Consequent PIN1 Binding. 2922 33

Peptidylprolyl isomerase A (PPIA) has been reported to be correlated with cancer. The present study investigated the prognostic values of PPIA expression levels in cancer by comparing different types of cancer using databases. High expression levels of PPIA were observed in 17 out of 17 cancer types compared with normal adjacent tissues. High expression levels of PPIA were associated with decreased overall survival in low grade glioma, acute myeloid leukemia, lung adenocarcinoma, skin cutaneous melanoma and liver hepatocellular carcinoma (LIHC). The prognostic effect of PPIA expression in LIHC was independent of tumor grade. High expression levels of PPIA were of particular prognostic value in stage 3, American Joint Committee on Cancer Tumor 3, hepatitis B virus negative and sorafenib-administered subgroups in LIHC. The expression level of PPIA was significantly associated with levels of basigin and signal transducer and activator of transcription 3, which may be major effectors of PPIA in the progression of the cancer.
 ...
PMID:High expression level of peptidylprolyl isomerase A is correlated with poor prognosis of liver hepatocellular carcinoma. 3161 78