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 role of genomic instability in the development of squamous cell carcinoma (SCCHN) has become apparent with the publication of three major allelotype analysis of this disease, as well as many publications which have concentrated on specific target regions. The measurement of accumulated genetic alterations or fractional allele loss, as determined by allelotype analysis, provides a useful molecular indicator of tumour behaviour. In one major study, a positive correlation was found between FAL > median value and lymph node metastasis and also with a poor clinical outcome. In addition the recognition of microsatellite instability as a marker of DNA repair defects has provided a further molecular marker of the disease process and that loss of heterozygosity analysis and microsatellite instability appear to be independent genetic events in the development of SCCHN. Furthermore, the recognition of a number of novel target regions in SCCHN on chromosome arms, 1 p, 3p, 8p, 9p, 13q, 17p and 18q and our understanding of the role of certain oncogenes and tumour suppressor genes and their interaction with human papillomavirus has provided further elucidation of the neoplastic process. Even though this review describes a number of molecular events in SCCHN, the sequence of events still eludes the scientific community at present.
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PMID:Genomic instability in squamous cell carcinoma of the head and neck. 881 45

The tumour suppressor p53 plays a crucial role in the cellular response to DNA damage. The p53 protein is able both to detect sites of DNA damage and to interact with DNA in a sequence-specific manner and function in the regulation of target gene expression. These two properties map to discrete functional domains of the protein, the C-terminus and the central core domain respectively. They are essential for integration of a normal cellular response to DNA damage, with initiation of either G1 cell cycle arrest or apoptosis. This review considers the domain structure of p53 in relation to the protein's various functions, together with the importance of tertiary structure and conformational flexibility. The precise regulation of p53 function remains to be established, although the protein is known to be phosphorylated/de-phosphorylated by a number of specific protein kinases/phosphatases. A recent discovery indicates that p53 may be activated by autoproteolysis and that proteolytic cleavage is induced by direct interaction with sites of DNA damage. This process is reminiscent of the bacterial Lex A system and would provide one mechanism for activation of p53 in response to cellular DNA damage.
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PMID:Structures and functions of the tumor suppressor p53. 976 43