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 development of oral and head and neck squamous cell carcinomas occurs in relation with multiple events including mainly: loss of cycle cell control, evasion from apoptosis, telomerase reactivation. Complex interactions between a set of molecules, cell cycle proteins, tumour suppressor genes, oncogenes and the telomerase, occur in the multiple step process of carcinogenesis. The 2 main ways of control of the cell cycle rely on 2 tumour suppressor genes: the P53 gene and the retinoblastoma gene or RB gene. One of the regulation pathways or the 2 regulation pathways are disabled during the development of oral and head and neck squamous cell carcinomas. Most of the time, the inactivation of the P53 pathway results from a loss of function of the p53 protein, secondary to mutation and/or deletion of the P53 gene; It may also result of the amplification of the MDM2 gene and of the inactivation of the arf protein. The RB pathway leads to cell proliferation by loss of the p16 protein, by amplification of the cyclin D1 gene and less frequently by mutation of the RB gene or loss of the retinoblastoma protein. In India and South-East Asia, the activation of RAS and MYC oncogenes appears to be related with the presence of specific carcinogens in snuff and tobacco. By blocking apoptosis, the Bcl2 protein seems to increase the resistance of tumours to radiotherapy and chemotherapy.
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PMID:[Genic alterations in oral and head and neck squamous cell carcinomas: analysis of international literature]. 1278

CD4+CD56+ haematodermic neoplasms (HDN) constitute a rare disease characterized by aggressive clinical behaviour and a poor prognosis. Tumour cells from HDN are leukaemic counterparts of plasmacytoid dendritic cells (pDCs). Despite increased knowledge of the ontogenetic origin of these tumours, the genetic causes and oncogenic signalling events involved in malignant transformation are still unknown. To delineate novel candidate regions and disease-related genes, we studied nine typical CD4+CD56+ HDN cases using genome-wide high-resolution array comparative genomic hybridization (CGH). Genomic imbalances, which were predominantly losses, were frequently detected. Gross genomic losses or gains involving an entire chromosome were observed in eight cases. The most frequent imbalances were deletions of chromosome 9, chromosome 13 and partial losses affecting 17p or 12p. Combinations of deletions of tumour suppressor genes (TSG), namely RB1, CDKN1B (p27), CDKN2A, (p16(ink4a), p14(arf)) or TP53 (p53), were observed in all cases. These results indicate that deletion events altering G1/S regulation are crucial for HDN oncogenesis. Furthermore, in addition to frequent sporadic gene losses, in one case we observed a 8q24 interstitial deletion that brought MYC closer to miR-30b/miR-30d, which may be related to their deregulation. Taken together, these results indicate that in addition to frequent G1/S checkpoint alterations, various genetic events could contribute to the chemoresistance of the tumour.
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PMID:Recurrent genomic aberrations combined with deletions of various tumour suppressor genes may deregulate the G1/S transition in CD4+CD56+ haematodermic neoplasms and contribute to the aggressiveness of the disease. 1915 33

Persistent hyperplastic primary vitreous (PHPV), also known as persistent fetal vasculature, is a rare congenital developmental malformation of the eye, caused by the failure of regression of the primary vitreous. It is divided into anterior and posterior types and is characterized by the presence of a vascular membrane located behind the lens. The condition can be of an isolated type or can occur with other ocular disorders. Most cases of PHPV are sporadic, but it can be inherited as an autosomal dominant or recessive trait. Inherited PHPV also occurs in several breeds of dogs and cats. In a limited number of cases, Norrie disease and FZD4 genes are found to be mutated in unilateral and bilateral PHPV. These genes when mutated also cause Norrie disease pseudoglioma and familial exudative vitreoretinopathy that share some of the clinical features with PHPV. Mice lacking arf and p53 tumour suppressor genes as well as Norrie disease pseudoglioma and LRP5 genes suggest that these genes are needed for hyaloid vascular regression. These experiments also indicate that abnormalities in normal apoptosis and defects in Wnt signalling pathway may be responsible for the pathogenesis of PHPV. Identification of other candidate genes in the future may provide a better understanding of the pathogenesis of the condition that may lead to a better therapeutic approach and better management.
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PMID:Persistent hyperplastic primary vitreous: congenital malformation of the eye. 2009 98

The ARF tumour suppressor protein, the gene of which is frequently mutated in many human cancers, plays an important role in the cellular stress response by orchestrating up-regulation of p53 protein and consequently promoting cell-cycle delay. Although p53 protein function has been clearly linked to the cellular DNA damage response, the role of ARF protein in this process is unclear. Here, we report that arf gene transcription is induced by DNA strand breaks (SBs) and that ARF protein accumulates in response to persistent DNA damage. We discovered that poly(ADP-ribose) synthesis catalysed by PARP1 at the sites of unrepaired SBs activates ARF transcription through a protein signalling cascade, including the NAD(+)-dependent deacetylase SIRT1 and the transcription factor E2F1. Our data suggest that poly(ADP-ribose) synthesis at the sites of SBs initiates DNA damage signal transduction by reducing the cellular concentration of NAD(+), thus down-regulating SIRT1 activity and consequently activating E2F1-dependent ARF transcription. Our findings suggest a vital role for ARF in DNA damage signalling, and furthermore explain the critical requirement for ARF inactivation in cancer cells, which are frequently deficient in DNA repair and accumulate DNA damage.
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PMID:ARF induction in response to DNA strand breaks is regulated by PARP1. 2429 53