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Catalytic subunit of protein phosphatase 6 (PP6). PP6 is a component of a signaling pathway regulating cell cycle progression in response to IL2 receptor stimulation. N-terminal domain restricts G1 to S phase progression in cancer cells, in part through control of cyclin D1. During mitosis, regulates spindle positioning. Downregulates MAP3K7 kinase activation of the IL1 signaling pathway by dephosphorylation of MAP3K7. Participates also in the innate immune defense against viruses by desphosphorylating RIG-I/DDX58, an essential step that triggers RIG-I/DDX58-mediated signaling activation.
Gene References into Functions
PP6 rapidly interacts with ASK3 in an osmolality-dependent manner, and it inactivates ASK3 to induce RVI and, thereby, cell survival under hyperosmotic stress. PMID: 29539411
findings define the WHIP-TRIM14-PPP6C mitochondrial signalosome required for RIG-I-mediated innate antiviral immunity. PMID: 29053956
findings suggest that BRCA1 is a novel modulator of PP6 signalling via its interaction with ANKRD28. PMID: 27026398
Data show 408 phosphopeptides on 272 proteins that increased and 298 phosphopeptides on 220 proteins that decreased in phosphorylation upon catalytic subunit of rotein phosphatase 6 (PP6c) depletion in mitotic cells. PMID: 26462736
Protein phosphatase 6 (ppp6c), a negative regulator that restricts the G1 to S phase progression, is diminished in human psoriatic epidermis and is directly targeted by miR-31. PMID: 26138368
PP6 is involved in a diverse set of biological pathways. PMID: 25999147
These results suggest that human PP6 interacts with and positively regulates the activity of the influenza A virus RNA-dependent RNA polymerase. PMID: 25187537
PP6C mutations have distinct functional and clinical consequences in melanoma, and confer sensitivity to Aurora A kinase inhibitors. PMID: 24336958
PP6c associates with E-cadherin in adherens junctions and is required to oppose casein kinase-1 to maintain cell surface localization of E-cadherin. PMID: 24063632
Findings support the view that formation of micronuclei rather than chromosome instability alone explains how loss of PPP6C, and more generally mitotic spindle and centrosome defects, can act as drivers for genome instability in melanoma. PMID: 23729733
Results show that Sit4p and its mammalian orthologue, PP6, regulate traffic from the ER to the Golgi complex which is consistent with its role in coat recycling. PMID: 23864707
miR-373 can regulate cell cycle progression by targeting PPP6C transcripts and promotes the growth activity of HCC cells in vitro. The downregulation of PPP6C by miR-373 may explain why the expression of miR-373 can promote HCC cell proliferation. PMID: 21481188
PP6 is required for non-homologous end joining repair; its expression may harbor a protective role during the development of breast cancer tissues. PMID: 21451261
Results demonstrate a role for PP6 as the T-loop phosphatase regulating Aurora A activity bound to its activator TPX2 during mitotic spindle formation. PMID: 21187329
A novel function of DNA-PKcs is to recruit PP6 to sites of DNA damage and that PP6 contributes to the dephosphorylation of gamma-H2AX, the dissolution of ionizing radiation-induced foci, and release from the G(2)/M checkpoint in vivo. PMID: 20065038
Protein phosphatase 6 subunit with conserved Sit4-associated protein domain targets IkappaBepsilon PMID: 16769727
PP6 regulates cell cycle progression in human cells at least in part through control of cyclin D1 and the function of PP6 is distinct from its homolog Sit4 in yeast. PMID: 17568194
Our data demonstrate that protein phosphatase-6 associates with and activates DNA-PK in response to ionizing radiation. PMID: 19198648
results illustrate that the human PP6-associated proteins are capable of providing distinct rapamycin-sensitive and Sit4-dependent Sap functions in the heterologous context of the yeast cell PMID: 19621075
our results seem to discard the role of the previously described polymorphisms in SERPINE2, PPP6C and PBX3 in celiac disease susceptibility. PMID: 19626039
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Subcellular Location
Mitochondrion. Cytoplasm.
Protein Families
PPP phosphatase family, PP-6 (PP-V) subfamily
Tissue Specificity
Ubiquitously expressed in all tissues tested with highest expression levels in testis, heart, kidney, brain, stomach, liver and skeletal muscle and lowest in placenta, lung colon and spleen.