Protein phosphatase 1 regulatory subunit 15A

Definition:

Recruits the serine/threonine-protein phosphatase PPP1CA to prevents excessive phosphorylation of the translation initiation factor eIF-2A/EIF2S1, thereby reversing the shut-off of protein synthesis initiated by stress-inducible kinases and facilitating recovery of cells from stress. Down-regulates the TGF-beta signaling pathway by promoting dephosphorylation of TGFB1 by PP1. May promote apoptosis by inducing p53/TP53 phosphorylation on 'Ser-15'. Plays an essential role in autophagy by tuning translation during starvation, thus enabling lysosomal biogenesis and a sustained autophagic flux. Acts also a viral restriction factor by attenuating HIV-1 replication. Mechanistically, mediates the inhibition of HIV-1 TAR RNA-mediated translation.; (Microbial infection) Promotes enterovirus 71 replication by mediating the internal ribosome entry site (IRES) activity of viral 5'-UTR.

References:

[1]. Matthew H Brush, et al. Growth arrest and DNA damage-inducible protein GADD34 targets protein phosphatase 1 alpha to the endoplasmic reticulum and promotes dephosphorylation of the alpha subunit of eukaryotic translation initiation factor 2. Mol Cell Biol. 2003 Feb;23(4):1292-303. [Content Brief]

[2]. Gennaro Gambardella, et al. GADD34 is a modulator of autophagy during starvation. Sci Adv. 2020 Sep 25;6(39):eabb0205. [Content Brief]

[3]. Ayako Yagi, et al. GADD34 induces p53 phosphorylation and p21/WAF1 transcription. J Cell Biochem. 2003 Dec 15;90(6):1242-9. [Content Brief]

[4]. Meng S Choy, et al. Structural and Functional Analysis of the GADD34:PP1 eIF2α Phosphatase. Cell Rep. 2015 Jun 30;11(12):1885-91. [Content Brief]

[5]. Weibin Shi, et al. GADD34-PP1c recruited by Smad7 dephosphorylates TGFbeta type I receptor. J Cell Biol. 2004 Jan 19;164(2):291-300. [Content Brief]

[6]. Mohammad Ishaq, et al. GADD34 attenuates HIV-1 replication by viral 5'-UTR TAR RNA-mediated translational inhibition. Virology. 2020 Jan 15;540:119-131. [Content Brief]

[7]. Hui Li, et al. Enterovirus 71 Activates GADD34 via Precursor 3CD to Promote IRES-Mediated Viral Translation. Microbiol Spectr. 2022 Feb 23;10(1):e0138821. [Content Brief]

[8]. Celio X C Santos, et al. Targeted redox inhibition of protein phosphatase 1 by Nox4 regulates eIF2α-mediated stress signaling. EMBO J. 2016 Feb 1;35(3):319-34. [Content Brief]

[9]. Q Zhan, et al. The gadd and MyD genes define a novel set of mammalian genes encoding acidic proteins that synergistically suppress cell growth. Mol Cell Biol. 1994 Apr;14(4):2361-71. [Content Brief]

[10]. J H Connor, et al. Growth arrest and DNA damage-inducible protein GADD34 assembles a novel signaling complex containing protein phosphatase 1 and inhibitor 1. Mol Cell Biol. 2001 Oct;21(20):6841-50. [Content Brief]

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