Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.6.1.25 (triphosphatase)
 1,529 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The phosphatase PTEN (phosphatase and tensin homolog deleted on chromosome 10) antagonizes phosphoinositide 3-kinase (PI3K) signaling and is one of the most frequently mutated tumor suppressors in human cancers. Its regulation appears complex and is of great potential clinical importance. The protein P-REX2a (phosphatidylinositol 3,4,5-trisphosphate Rac exchanger 2a), better known as a regulator of the small guanosine triphosphatase Rac, has been identified as a direct regulator of PTEN activity and as a potential oncoprotein. P-REX2a can stimulate cell proliferation by inhibiting PTEN and stimulating downstream PI3K-dependent signaling. This suggests that aberrant control of PTEN by P-REX2a may represent a key tumorigenic mechanism, in agreement with recent studies supporting the pathological relevance of several other proposed PTEN regulators.
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PMID:P-REX2a driving tumorigenesis by PTEN inhibition. 1986 88

Up to one-third of human melanomas are characterized by an oncogenic mutation in the gene encoding the small guanosine triphosphatase (GTPase) NRAS. Ras proteins activate three primary classes of effectors, namely, Rafs, phosphatidyl-inositol-3-kinases (PI3Ks) and Ral guanine exchange factors (RalGEFs). In melanomas lacking NRAS mutations, the first two effectors can still be activated through an oncogenic BRAF mutation coupled with a loss of the PI3K negative regulator PTEN. This suggests that Ras effectors promote melanoma, regardless of whether they are activated by oncogenic NRas. The only major Ras effector pathway not explored for its role in melanoma is the RalGEF-Ral pathway, in which Ras activation of RalGEFs converts the small GTPases RalA and RalB to an active guanosine triphosphate-bound state. We report that RalA is activated in several human melanoma cancer cell lines harboring an oncogenic NRAS allele, an oncogenic BRAF allele or wild-type NRAS and BRAF alleles. Furthermore, short hairpin RNA (shRNA)-mediated knockdown of RalA, and to a lesser extent of RalB, variably inhibited the tumorigenic growth of melanoma cell lines having these three genotypes. Thus, as is the case for Raf and PI3 K signaling, Rals also contribute to melanoma tumorigenesis.
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PMID:Ral activation promotes melanomagenesis. 2056 21

Senescent and damaged mitochondria undergo selective mitophagic elimination through mechanisms requiring two Parkinson's disease factors, the mitochondrial kinase PINK1 (PTEN-induced putative kinase protein 1; PTEN is phosphatase and tensin homolog) and the cytosolic ubiquitin ligase Parkin. The nature of the PINK-Parkin interaction and the identity of key factors directing Parkin to damaged mitochondria are unknown. We show that the mitochondrial outer membrane guanosine triphosphatase mitofusin (Mfn) 2 mediates Parkin recruitment to damaged mitochondria. Parkin bound to Mfn2 in a PINK1-dependent manner; PINK1 phosphorylated Mfn2 and promoted its Parkin-mediated ubiqitination. Ablation of Mfn2 in mouse cardiac myocytes prevented depolarization-induced translocation of Parkin to the mitochondria and suppressed mitophagy. Accumulation of morphologically and functionally abnormal mitochondria induced respiratory dysfunction in Mfn2-deficient mouse embryonic fibroblasts and cardiomyocytes and in Parkin-deficient Drosophila heart tubes, causing dilated cardiomyopathy. Thus, Mfn2 functions as a mitochondrial receptor for Parkin and is required for quality control of cardiac mitochondria.
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PMID:PINK1-phosphorylated mitofusin 2 is a Parkin receptor for culling damaged mitochondria. 2384 46