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 phosphoprotein associates with proteins involved in DNA replication, transcription, cell cycle machinery and regulation of its own expression. Recently it has been shown that p53 can also bind to trk A tyrosine kinase which is the receptor for nerve growth factor (NGF). This study demonstrates that p53 appears to associate with trk A via c-abl. Endogenous c-abl was detected when the trk A and p53 complex was immunoprecipitated from lysates of NGF stimulated NIH3T3 cells expressing trk A or NIH3T3 cells expressing trk A and a temperature sensitive p53 (val 135). Endogenous c-abl and trk A association was observed in NGF stimulated p53 negative fibroblasts transfected with trk A alone; suggesting that c-abl can independently bind to trk A in the absence of p53. Interestingly, association between endogenous p53 and trk A was not detected in NGF stimulated abl negative fibroblasts transfected with trk A or when these cells were exposed to gamma radiation. This result suggests that p53 preferentially binds to trk A in the presence of c-abl and that p53 and trk A do not appear to associate directly even if p53 is activated and its levels increased by gamma radiation. Overall, these data suggest that c-abl is possibly acting as an adaptor or bridge between p53 and trk A. Oncogene (2000).
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PMID:c-abl is involved in the association of p53 and trk A. 1087 55

Our previous study demonstrated a correlation between increased apoptotic index in pre-radiotherapy cervical cancer and poor patient survival. Apoptosis may thus play an important role in the response of cervical cancer to radiation. Most of cervical carcinomas are associated with human papillomavirus (HPV), and the oncoproteins E6 and E7 disrupt the functions of tumour suppressor genes, resulting in genetic alteration. To understand the multiple genetic changes related to cell radiosensitivity and the induction of apoptosis, two cervical cancer cell lines, SiHa (with HPV infection) and C-33A (contains a mutant p53 gene), were selected for present studied. The gene expression patterns in these cell lines were compared before and after radiation. When compared to normal cervical tissues, differential expressions were observed in 46 genes among the two cell lines studied. Thirty-three genes showed altered expressions after radiation induction. Three out of ten genes that showed differential responsiveness to radiation in the two cell lines were further confirmed by reverse transcriptase-polymerase chain reaction (RT-PCR). Bak and c-abl were found to be potential genes that may play important roles in signaling apoptosis in cervical cancer cells following radiation induction.
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PMID:Differential gene expression in cervical cancer cell lines before and after ionizing radiation. 1268 76