title: IRE1 phosphatase PP2Ce regulates adaptive ER stress response in the postpartum mammary gland.
abstract: We recently reported that the PPM1l gene encodes an endoplasmic reticulum (ER) membrane targeted protein phosphatase (named PP2Ce) with highly specific activity towards Inositol-requiring protein-1 (IRE1) and regulates the functional outcome of ER stress. In the present report, we found that the PP2Ce protein is highly expressed in lactating epithelium of the mammary gland. Loss of PP2Ce in vivo impairs physiological unfolded protein response (UPR) and induces stress kinase activation, resulting in loss of milk production and induction of epithelial apoptosis in the lactating mammary gland. This study provides the first in vivo evidence that PP2Ce is an essential regulator of normal lactation, possibly involving IRE1 signaling and ER stress regulation in mammary epithelium.
authors.affiliation: Department of Anesthesiology, Division of Molecular Medicine, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, United States of America.
authors.forename: Shuxun
authors.initials: S
authors.lastname: Ren
authors.affiliation: Department of Anesthesiology, Division of Molecular Medicine, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, United States of America.
authors.forename: Gang
authors.initials: G
authors.lastname: Lu
authors.affiliation: Department of Anesthesiology, Division of Molecular Medicine, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, United States of America.
authors.forename: Asuka
authors.initials: A
authors.lastname: Ota
authors.affiliation: Departments of Microbiology, Immunology and Molecular Genetics, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, United States of America.
authors.forename: Z Hong
authors.initials: ZH
authors.lastname: Zhou
authors.affiliation: Department of Anesthesiology, Division of Molecular Medicine, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, United States of America; Departments of Physiology and Medicine, Cardiovascular Research Laboratories, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, United States of America.
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Vondriska
authors.affiliation: Departments of Obstetrics and Gynecology and Biological Chemistry, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, United States of America.
authors.forename: Timothy F
authors.initials: TF
authors.lastname: Lane
authors.affiliation: Department of Anesthesiology, Division of Molecular Medicine, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, United States of America; Departments of Physiology and Medicine, Cardiovascular Research Laboratories, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, United States of America.
authors.forename: Yibin
authors.initials: Y
authors.lastname: Wang
mesh_terms: D000818:Animals; D017209:Apoptosis; D059865:Endoplasmic Reticulum Stress; D005260:Female; D006801:Humans; D007774:Lactation; D008321:Mammary Glands, Animal / Q000166:cytology / Q000502:physiology* / Q000648:ultrastructure; D008565:Membrane Proteins / Q000378:metabolism*; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010749:Phosphoprotein Phosphatases / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D049590:Postpartum Period; D000071636:Protein Phosphatase 2C; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D015398:Signal Transduction; D056811:Unfolded Protein Response
chemical_list: D008565:Membrane Proteins; C486556:Ern2 protein, mouse; D017346:Protein Serine-Threonine Kinases; D010749:Phosphoprotein Phosphatases; D000071636:Protein Phosphatase 2C