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CReP deletion activates a linear signaling pathway involving eIF2alpha phosphorylation, ATF4 translation, and FGF21 induction, which promotes increased energy expenditure, and subsequently improved obesity-related metabolic parameters.
Results highlighted the essential roles played by GADD34 and CReP in regulating mRNA translation during unstressed conditions and following endoplasmic reticulum stress.
CReP expression was markedly suppressed in XBP1-deficient mice livers due to hyperactivated Ire1alpha.
Ppp1r15a mutant mice are superficially indistinguishable from wild type; Ppp1r15b(-/-) mouse embryos survive gestation but exhibit severe growth retardation and impaired erythropoiesis, and loss of both Ppp1r15 genes leads to early embryonic lethality
p97-mediated degradation, together with a reduction in CReP synthesis, is essential for timely stress-induced reduction of CReP levels and, consequently, for robust eIF2alpha phosphorylation to enforce the stress response.
Whole-exome sequencing identified a homozygous missense mutation, c.1972G>A; p.Arg658Cys, in protein phosphatase 1, regulatory subunit 15b (PPP1R15B)
the first homozygous mutation in the PPP1R15B gene encoding the regulatory subunit of an eIF2alpha-specific phosphatase in two siblings affected by a novel syndrome of diabetes of youth with short stature, intellectual disability, and microcephaly
CIP2A regulates cancer metabolism and CREB phosphorylation in non-small cell lung cancer
the mammalian traffic machinery co-opts p-eIF2alpha and CReP, regulators of translation initiation.
PPP1R15B promotes dephosphorylation of the transcription initiation factor EIF2-alpha (EIF2S1\; MIM 603907) through recruitment of protein phosphatase-1 (PP1) catalytic subunits (see MIM 176875) (Harding et al., 2009
constitutive repressor of eIF2alpha phosphorylation
, protein phosphatase 1 regulatory subunit 15B
, protein phosphatase 1, regulatory (inhibitor) subunit 15B
, protein phosphatase 1, regulatory (inhibitor) subunit 15b