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

Shuxun Ren; Gang Lu; Asuka Ota; Z. Hong Zhou; Thomas M. Vondriska; Timothy F Lane; Yibin Wang

doi:10.1371/journal.pone.0111606

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

Shuxun Ren, Gang Lu, Asuka Ota, Z. Hong Zhou, Thomas M. Vondriska, Timothy F Lane, Yibin Wang

Medical Education

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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.

Original language	English (US)
Article number	e111606
Journal	PloS one
Volume	9
Issue number	11
DOIs	https://doi.org/10.1371/journal.pone.0111606
State	Published - Nov 2014

Funding

This work is supported in part by NIH (HL070079 for YW), an NIH Ruth L. Kirschstein National Research Service Award (AO). The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. The authors wish to acknowledge the excellent technical support from Ms. Haiying Pu in this study.

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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.",

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AU - Lu, Gang

AU - Ota, Asuka

AU - Zhou, Z. Hong

AU - Vondriska, Thomas M.

AU - Lane, Timothy F

AU - Wang, Yibin

N1 - Publisher Copyright: © 2014 Ren et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

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

Abstract

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