PTEN: a protein that plays a crucial role in various cellular processes

NCBI ID: G5728

PTEN

PTEN: a protein that plays a crucial role in various cellular processes

Several studies have investigated the function and regulation of PTEN in different contexts.

One viewpoint is that PTEN can inhibit glucose uptake in cells by blocking the recycling of the glucose transporter GLUT1 to the plasma membrane. This process is mediated by PTEN's interaction with SNX27 and VPS26 retromer complex.

In breast cancer cells, overexpression of a protein called IRIS can repress the transcription of the PTEN gene, resulting in low levels of PTEN protein. This, in turn, activates AKT and inhibits HIF-1alpha phosphorylation, leading to the accumulation of HIF-1alpha and the expression of its target genes involved in metastasis.

In another study, it was found that UBE2E1 can ubiquitinate PTEN and mark it for degradation. Knockdown of UBE2E1 rescues PTEN levels, suggesting that UBE2E1 plays a role in PTEN stability.

The methylation status of the SALL2 gene can also affect the expression of PTEN in breast cancer cells. Hypomethylation of SALL2 leads to PTEN upregulation, inhibiting Akt/mTOR signaling and resulting in estrogen-dependent growth and tamoxifen sensitivity. Conversely, hypermethylation of SALL2 represses PTEN expression, activating Akt/mTOR signaling and leading to estrogen-independent tumor growth and tamoxifen resistance.

Finally, PTEN, along with PLCXD, counteracts endosomal accumulation of a lipid called PtdIns(4,5)P2 in the absence of OCRL. PTEN increases PtdIns(4,5)P2 levels, while OCRL and PLC directly decrease these levels. Thus, the balance between PTEN, OCRL, and PLCXD is crucial for regulating PtdIns(4,5)P2 metabolism and maintaining normal cellular function.

Overall, PTEN's diverse functions in cellular processes, including glucose uptake, metastasis, stability regulation, and lipid metabolism, highlight its significance in various biological contexts.
From the provided context information, the following key viewpoints can be extracted regarding PTEN:

PTEN loss or inhibition, as well as activation of AKT, can activate PI3K signaling, potentially repressing the expression of MHC molecules and their induction by IFN-gamma. This repression may hinder T-cell activation, tumor recognition, and anti-tumor immunity.
Inhibition of PTEN can lead to increased stability of IP3R3, promoting apoptosis in response to IP3 production. PTEN competes with FBXL2 for IP3R3 binding, enhancing its stability and mitochondrial Ca2+ response, ultimately facilitating apoptosis.
Ectopic overexpression of FDPS in PTEN-deficient prostate cancer cells increases proliferation and growth advantage.
Inhibition of ROR1, combined with erlotinib treatment, can decrease AKT/mTOR signaling pathway activity and enhance cell apoptosis while reducing cell proliferation and survival.
Upregulation of miR-21 can lead to the downregulation of various target genes including PTEN. PTEN negatively regulates the PI3K/AKT/mTOR pathway, controlling cell survival, growth, and differentiation.

These key viewpoints demonstrate the diverse roles and impacts of PTEN in different cellular processes and cancer-related pathways.

Protein Name: Phosphatase And Tensin Homolog

Functions: Acts as a dual-specificity protein phosphatase, dephosphorylating tyrosine-, serine- and threonine-phosphorylated proteins (PubMed:9187108, PubMed:9256433). Also acts as a lipid phosphatase, removing the phosphate in the D3 position of the inositol ring from phosphatidylinositol 3,4,5-trisphosphate, phosphatidylinositol 3,4-diphosphate, phosphatidylinositol 3-phosphate and inositol 1,3,4,5-tetrakisphosphate with order of substrate preference in vitro PtdIns(3,4,5)P3 > PtdIns(3,4)P2 > PtdIns3P > Ins(1,3,4,5)P4 (PubMed:16824732, PubMed:26504226, PubMed:9593664). Tumor suppressor, the lipid phosphatase activity is critical for its tumor suppressor function (PubMed:9187108, PubMed:9616126, PubMed:9811831). Antagonizes the PI3K-AKT/PKB signaling pathway by dephosphorylating phosphoinositides and thereby modulating cell cycle progression and cell survival (PubMed:31492966). The unphosphorylated form cooperates with MAGI2 to suppress AKT1 activation (PubMed:11707428). In motile cells, suppresses the formation of lateral pseudopods and thereby promotes cell polarization and directed movement (PubMed:22279049). Dephosphorylates tyrosine-phosphorylated focal adhesion kinase and inhibits cell migration and integrin-mediated cell spreading and focal adhesion formation (PubMed:22279049). Required for growth factor-induced epithelial cell migration; growth factor stimulation induces PTEN phosphorylation which changes its binding preference from the p85 regulatory subunit of the PI3K kinase complex to DLC1 and results in translocation of the PTEN-DLC1 complex to the posterior of migrating cells to promote RHOA activation (PubMed:26166433). Meanwhile, TNS3 switches binding preference from DLC1 to p85 and the TNS3-p85 complex translocates to the leading edge of migrating cells to activate RAC1 activation (PubMed:26166433). Plays a role as a key modulator of the AKT-mTOR signaling pathway controlling the tempo of the process of newborn neurons integration during adult neurogenesis, including correct neuron positioning, dendritic development and synapse formation (By similarity). Involved in the regulation of synaptic function in excitatory hippocampal synapses. Recruited to the postsynaptic membrane upon NMDA receptor activation, is required for the modulation of synaptic activity during plasticity. Enhancement of lipid phosphatase activity is able to drive depression of AMPA receptor-mediated synaptic responses, activity required for NMDA receptor-dependent long-term depression (LTD) (By similarity). May be a negative regulator of insulin signaling and glucose metabolism in adipose tissue. The nuclear monoubiquitinated form possesses greater apoptotic potential, whereas the cytoplasmic nonubiquitinated form induces less tumor suppressive ability (PubMed:10468583, PubMed:18716620)

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