Publications by authors named "Nevin M Perera"
The tumor suppressor phosphatase and tensin homolog deleted on chromosome 10 (PTEN) has a well-characterized lipid phosphatase activity and a poorly characterized protein phosphatase activity. We show that both activities are required for PTEN to inhibit cellular invasion and to mediate most of its largest effects on gene expression. PTEN appears to dephosphorylate itself at threonine 366, and mutation of this site makes lipid phosphatase activity sufficient for PTEN to inhibit invasion.
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- PTEN is a tumor suppressor that regulates cell signaling by deactivating a specific lipid called PtdInsP(3), and its function can be influenced by how it is tagged with ubiquitin, which can alter its location and stability in cells.
- The study reveals that the location of PTEN at the plasma membrane increases its ubiquitination, and although phosphorylation helps stabilize PTEN, it doesn’t prevent ubiquitination directly.
- Additionally, under hyperosmotic stress, PTEN gets ubiquitinated, which raises the levels of PtdInsP(3) before PTEN levels drop, suggesting that ubiquitination serves as a reversible regulatory process for PTEN activity.
Article Synopsis
- PTEN is a key tumor suppressor frequently mutated in cancers, but its loss of expression often occurs without mutations in many tumors.
- It gets phosphorylated on specific sites by enzymes GSK3 and CK2, and blocking these phosphorylation events can be done with specific inhibitors in cell cultures.
- In studies on glioblastoma cell lines, inhibiting phosphorylation at Thr366 either by mutation or through GSK3 inhibitors resulted in a more stable PTEN protein, suggesting phosphorylation at this site destabilizes PTEN.
In obesity and diabetes, the ability of hypothalamic neurons to sense and transduce changes in leptin and insulin levels is compromised. The effects of both hormones require intracellular signalling via the PI3-kinase pathway, which is inhibited by the phosphatase PTEN. We show that leptin-stimulated F-actin depolymerization in mouse hypothalamic cells is inhibited by PTEN, a process involving independent effects of both its lipid and protein phosphatase activities.
View Article and Find Full Text PDFThe PTEN (phosphatase and tensin homologue deleted on chromosome 10) tumour-suppressor protein is a phosphoinositide 3-phosphatase which antagonizes phosphoinositide 3-kinase-dependent signalling by dephosphorylating PtdIns(3,4,5)P3. Most tumour-derived point mutations of PTEN induce a loss of function, which correlates with profoundly reduced catalytic activity. However, here we characterize a point mutation at the N-terminus of PTEN, K13E from a human glioblastoma, which displayed wild-type activity when assayed in vitro.
View Article and Find Full Text PDFPolyphosphoinositide-specific phospholipases (PICs) of the delta-subfamily are ubiquitous in eukaryotes, but an inability to control these enzymes physiologically has been a major obstacle to understanding their cellular function(s). Plc1p is similar to metazoan delta-PICs and is the only PIC in Saccharomyces cerevisiae. Genetic studies have implicated Plc1p in several cell functions, both nuclear and cytoplasmic.
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