Serine/threonine-protein phosphatase 5

Definition:

Serine/threonine-protein phosphatase that dephosphorylates a myriad of proteins involved in different signaling pathways including the kinases CSNK1E, ASK1/MAP3K5, PRKDC and RAF1, the nuclear receptors NR3C1, PPARG, ESR1 and ESR2, SMAD proteins and TAU/MAPT. Implicated in wide ranging cellular processes, including apoptosis, differentiation, DNA damage response, cell survival, regulation of ion channels or circadian rhythms, in response to steroid and thyroid hormones, calcium, fatty acids, TGF-beta as well as oxidative and genotoxic stresses. Participates in the control of DNA damage response mechanisms such as checkpoint activation and DNA damage repair through, for instance, the regulation ATM/ATR-signaling and dephosphorylation of PRKDC and TP53BP1. Inhibits ASK1/MAP3K5-mediated apoptosis induced by oxidative stress. Plays a positive role in adipogenesis, mainly through the dephosphorylation and activation of PPARG transactivation function (By similarity). Also dephosphorylates and inhibits the anti-adipogenic effect of NR3C1 (By similarity). Regulates the circadian rhythms, through the dephosphorylation and activation of CSNK1E. May modulate TGF-beta signaling pathway by the regulation of SMAD3 phosphorylation and protein expression levels. Dephosphorylates and may play a role in the regulation of TAU/MAPT. Through their dephosphorylation, may play a role in the regulation of ions channels such as KCNH2 (By similarity). Dephosphorylate FNIP1, disrupting interaction with HSP90AA1/Hsp90.

References:

[1]. Alex von Kriegsheim, et al. Regulation of the Raf-MEK-ERK pathway by protein phosphatase 5. Nat Cell Biol. 2006 Sep;8(9):1011-6. [Content Brief]

[2]. Ji Zhang, et al. Protein phosphatase 5 is required for ATR-mediated checkpoint activation. Mol Cell Biol. 2005 Nov;25(22):9910-9. [Content Brief]

[3]. Ambereen Ali, et al. Requirement of protein phosphatase 5 in DNA-damage-induced ATM activation. Genes Dev. 2004 Feb 1;18(3):249-54. [Content Brief]

[4]. Yoonsung Kang, et al. Protein phosphatase 5 is necessary for ATR-mediated DNA repair. Biochem Biophys Res Commun. 2011 Jan 7;404(1):476-81. [Content Brief]

[5]. Fei Liu, et al. Dephosphorylation of tau by protein phosphatase 5: impairment in Alzheimer's disease. J Biol Chem. 2005 Jan 21;280(3):1790-6. [Content Brief]

[6]. Thomas Wechsler, et al. DNA-PKcs function regulated specifically by protein phosphatase 5. Proc Natl Acad Sci U S A. 2004 Feb 3;101(5):1247-52. [Content Brief]

[7]. Kazuhiro Ikeda, et al. Protein phosphatase 5 is a negative regulator of estrogen receptor-mediated transcription. Mol Endocrinol. 2004 May;18(5):1131-43. [Content Brief]

[8]. David L Bruce, et al. Protein phosphatase 5 modulates SMAD3 function in the transforming growth factor-β pathway. Cell Signal. 2012 Nov;24(11):1999-2006. [Content Brief]

[9]. Rebecca A Sager, et al. Post-translational Regulation of FNIP1 Creates a Rheostat for the Molecular Chaperone Hsp90. Cell Rep. 2019 Jan 29;26(5):1344-1356.e5. [Content Brief]

[10]. Yoonsung Kang, et al. Protein phosphatase 5 regulates the function of 53BP1 after neocarzinostatin-induced DNA damage. J Biol Chem. 2009 Apr 10;284(15):9845-53. [Content Brief]

[11]. Yusuke Sekine, et al. The Kelch repeat protein KLHDC10 regulates oxidative stress-induced ASK1 activation by suppressing PP5. Mol Cell. 2012 Dec 14;48(5):692-704. [Content Brief]

[12]. M X Chen, et al. Activation of protein phosphatase 5 by limited proteolysis or the binding of polyunsaturated fatty acids to the TPR domain. FEBS Lett. 1997 Jan 2;400(1):136-40. [Content Brief]

[13]. Carrie L Partch, et al. Posttranslational regulation of the mammalian circadian clock by cryptochrome and protein phosphatase 5. Proc Natl Acad Sci U S A. 2006 Jul 5;103(27):10467-10472. [Content Brief]

[14]. Anindya Chatterjee, et al. Activated Rac1 GTPase translocates protein phosphatase 5 to the cell membrane and stimulates phosphatase activity in vitro. J Biol Chem. 2010 Feb 5;285(6):3872-3882. [Content Brief]

[15]. Fuminori Yamaguchi, et al. S100 proteins modulate protein phosphatase 5 function: a link between CA2+ signal transduction and protein dephosphorylation. J Biol Chem. 2012 Apr 20;287(17):13787-98. [Content Brief]

[16]. Tamás Zeke, et al. Human protein phosphatase 5 dissociates from heat-shock proteins and is proteolytically activated in response to arachidonic acid and the microtubule-depolymerizing drug nocodazole. Biochem J. 2005 Jan 1;385(Pt 1):45-56. [Content Brief]

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