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PLoS One. 2014 Nov 4;9(11):e111606. doi: 10.1371/journal.pone.0111606. eCollection 2014.

IRE1 phosphatase PP2Ce regulates adaptive ER stress response in the postpartum mammary gland.

Author information

1
Department of Anesthesiology, Division of Molecular Medicine, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, United States of America.
2
Departments of Microbiology, Immunology and Molecular Genetics, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, United States of America.
3
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.
4
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.

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.

PMID:
25369058
PMCID:
PMC4219728
DOI:
10.1371/journal.pone.0111606
[Indexed for MEDLINE]
Free PMC Article

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