ArticleMolecular metabolism2013
PPM1l encodes an inositol requiring-protein 1 (IRE1) specific phosphatase that regulates the functional outcome of the ER stress response.
Article in Molecular metabolism, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 38 citations in OpenAlex.
- Calcium-mediated calreticulin-IRE1α interaction drives dynamic fluctuation of IRE1α activity under chronic endoplasmic reticulum stress.Nature communications · 2026Article
- Signal Recognition Granule Receptor Beta Subunit Promotes Arrhythmogenic Remodeling in the Heart Failure Mice.Journal of the American Heart Association · 2026Article
- Exploring the IRE1 interactome: From canonical signaling functions to unexpected roles.The Journal of biological chemistry · 2024Review
- TGFβ1 regulates HRas-mediated activation of IRE1α through the PERK-RPAP2 axis in keratinocytes.Molecular carcinogenesis · 2022Article
- IRE1/XBP1 and endoplasmic reticulum signaling - from basic to translational research for cardiovascular disease.Current opinion in physiology · 2022Article
- Metal dependent protein phosphatase PPM family in cardiac health and diseases.Cellular signalling · 2021Review
- Competing endogenous RNA network analysis explores the key lncRNAs, miRNAs, and mRNAs in type 1 diabetes.BMC medical genomics · 2021Article
- Inhibition of the PI 3-kinase pathway disrupts the unfolded protein response and reduces sensitivity to ER stress-dependent apoptosis.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2020Article
- Mechanisms, regulation and functions of the unfolded protein response.Nature reviews. Molecular cell biology · 2020Review
- HAND1 loss-of-function within the embryonic myocardium reveals survivable congenital cardiac defects and adult heart failure.Cardiovascular research · 2020Article
- TGF-ß1 Induces Changes in the Energy Metabolism of White Adipose Tissue-Derived Human Adult Mesenchymal Stem/Stromal CellsMetabolites · 2020Article
- Pak2 as a Novel Therapeutic Target for Cardioprotective Endoplasmic Reticulum Stress Response.Circulation research · 2019Article
- The serine/threonine-protein kinase/endoribonuclease IRE1α protects the heart against pressure overload-induced heart failure.The Journal of biological chemistry · 2018Article
- Regulation of IRE1 RNase activity by the Ribonuclease inhibitor 1 (RNH1).Cell cycle (Georgetown, Tex.) · 2018Article
- AKT-mTOR signaling modulates the dynamics of IRE1 RNAse activity by regulating ER-mitochondria contacts.Scientific reports · 2017Article
- A Sarcoplasmic Reticulum Localized Protein Phosphatase Regulates Phospholamban Phosphorylation and Promotes Ischemia Reperfusion Injury in the Heart.JACC. Basic to translational science · 2017Article
- Inhibition of IRE1α-mediated XBP1 mRNA cleavage by XBP1 reveals a novel regulatory process during the unfolded protein response.Wellcome open research · 2017Article
- Adiposity Alters Genes Important in Inflammation and Cell Cycle Division in Human Cumulus Granulosa Cell.Reproductive sciences (Thousand Oaks, Calif.) · 2015Article
- Erratum: Proteostasis control by the unfolded protein response.Nature cell biology · 2015Article
- Proteostasis control by the unfolded protein response.Nature cell biology · 2015Review
Corrections and comments
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Authors and funding
12 authors at 1 institution in 1 country.
Funding
Abstract
The protein phosphatase 1-like gene (PPM1l) was identified as causal gene for obesity and metabolic abnormalities in mice. However, the underlying mechanisms were unknown. In this report, we find PPM1l encodes an endoplasmic reticulum (ER) membrane targeted protein phosphatase (PP2Ce) and has specific activity to basal and ER stress induced auto-phosphorylation of Inositol-REquiring protein-1 (IRE1). PP2Ce inactivation resulted in elevated IRE1 phosphorylation and higher expression of XBP-1, CHOP, and BiP at basal. However, ER stress stimulated XBP-1 and BiP induction was blunted while CHOP induction was further enhanced in PP2Ce null cells. PP2Ce protein levels are significantly induced during adipogenesis in vitro and are necessary for normal adipocyte maturation. Finally, we provide evidence that common genetic variation of PPM11 gene is significantly associated with human lipid profile. Therefore, PPM1l mediated IRE1 regulation and downstream ER stress signaling is a plausible molecular basis for its role in metabolic regulation and disorder.
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Registered trials
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