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 chromosome 9p21 region has been described to be frequently deleted in several neoplasias. The cyclin dependent kinase inhibitor 2A (CDKN2A or P16) gene was cloned in this region and identified as a tumour suppressor gene. However, much evidence indicates the existence of another tumour suppressor gene located proximal to the CDKN2A gene, which could be involved in cutaneous malignant melanoma (CMM) initiation. In the present report we have further investigated this 9p21 chromosomal region and cloned and characterised a novel gene within it (C9orf11). This gene shares no similarities to any known gene or predicted protein representing a novel human gene. Nevertheless, a putative leucine zipper pattern is located at the C-terminal end of the predicted protein, suggesting that it could dimerise. C9orf11 encodes for a protein of 294 amino acids with a predicted molecular mass of 32.8 kDa. C9orf11 is organised in eight exons that encompass a region of approx. 13 kb. Expression analysis demonstrates that C9orf11 is highly expressed in testis, although minor expression was seen in other tissues. Mutations in the C9orf11 gene were not detected in CMM families that were negative for CDKN2A mutations. Two SNPs for the C9orf11 gene have been identified, which could be used in segregation or association studies for other disorders.
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PMID:Isolation and characterisation of a novel human gene (C9orf11) on chromosome 9p21, a region frequently deleted in human cancer. 1111 25

The PTEN (phosphatase and tensin homologue deleted on chromosome 10) tumour suppressor is a phosphatidylinositol 3,4,5-trisphosphate [PtdIns(3,4,5)P(3)] 3-phosphatase that plays a critical role in regulating many cellular processes by antagonizing the phosphoinositide 3-kinase signalling pathway. We have identified and characterized two human homologues of PTEN, which differ with respect to their subcellular localization and lipid phosphatase activities. The previously cloned, but uncharacterized, TPTE (transmembrane phosphatase with tensin homology) is localized to the plasma membrane, but lacks detectable phosphoinositide 3-phosphatase activity. TPIP (TPTE and PTEN homologous inositol lipid phosphatase) is a novel phosphatase that occurs in several differentially spliced forms of which two, TPIP alpha and TPIP beta, appear to be functionally distinct. TPIP alpha displays similar phosphoinositide 3-phosphatase activity compared with PTEN against PtdIns(3,4,5)P(3), PtdIns(3,5)P(2), PtdIns(3,4)P(2) and PtdIns(3)P, has N-terminal transmembrane domains and appears to be localized on the endoplasmic reticulum. This is unusual as most signalling-lipid-metabolizing enzymes are not integral membrane proteins. TPIP beta, however, lacks detectable phosphatase activity and is cytosolic. TPIP has a wider tissue distribution than the testis-specific TPTE, with specific splice variants being expressed in testis, brain and stomach. TPTE and TPIP do not appear to be functional orthologues of the Golgi-localized and more distantly related murine PTEN2. We suggest that TPIP alpha plays a role in regulating phosphoinositide signalling on the endoplasmic reticulum, and might also represent a tumour suppressor and functional homologue of PTEN in some tissues.
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PMID:TPIP: a novel phosphoinositide 3-phosphatase. 1171 55

Recent work has shown that the LKB1 tumour suppressor protein kinase phosphorylates and activates protein kinases belonging to the AMP activated kinase (AMPK) subfamily. In this study, we identify the sucrose non-fermenting protein (SNF1)-related kinase (SNRK), a largely unstudied AMPK subfamily member, as a novel substrate for LKB1. We demonstrate that LKB1 activates SNRK by phosphorylating the T-loop residue (Thr173), and that the LKB1 regulatory subunits STRAD and MO25 are required for LKB1 to activate SNRK. We find that SNRK is not active when expressed in HeLa cells that lack expression of LKB1, and its activity is restored by expression of wild type LKB1, but not catalytically deficient LKB1. We also present evidence that two other AMPK-related kinases more distantly related to AMPK than SNRK, namely NIM1 and testis-specific serine/threonine kinase-1 (TSSK1) are not substrates for LKB1. Tissue distribution analysis indicates that SNRK protein is mainly expressed in testis, similar to TSSK isoforms, whereas NIM1 is more widely expressed. These results provide evidence that SNRK could mediate some of the physiological effects of LKB1.
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PMID:Identification of the sucrose non-fermenting related kinase SNRK, as a novel LKB1 substrate. 1573 51