Journal
FASEB JOURNAL
Volume 24, Issue 5, Pages 1541-1551Publisher
FEDERATION AMER SOC EXP BIOL
DOI: 10.1096/fj.09-149153
Keywords
sumoylation; MKP1; reactive oxygen species; pregnancy
Categories
Funding
- Wellcome Trust [084336]
- Institute of Obstetrics and Gynaecology (IOG) Trust
- National Institute for Health Research (NIHR) Biomedical Research Centre
- Cancer Research UK [12011] Funding Source: researchfish
Ask authors/readers for more resources
Survival of the conceptus is dependent on continuous progesterone signaling in the maternal decidua but how this is achieved under conditions of oxidative stress that characterize early pregnancy is unknown. Using primary cultures, we show that modest levels of reactive oxygen species (ROS) increase sumoylation in human endometrial stromal cells (HESCs), leading to enhanced modification and transcriptional inhibition of the progesterone receptor (PR). The ability of ROS to induce a sustained hypersumoylation response, or interfere with PR activity, was lost upon differentiation of HESCs into decidual cells. Hypersumoylation in response to modest levels of ROS requires activation of the JNK pathway. Although ROS-dependent JNK signaling is disabled on decidualization, the cells continue to mount a transcriptional response, albeit distinct from that observed in undifferentiated HESCs. We further show that attenuated JNK signaling in decidual cells is a direct consequence of altered expression of key pathway modulators, including induction of MAP kinase phosphatase 1 (MKP1). Overexpression of MKP1 dampens JNK signaling, prevents hypersumoylation, and maintains PR activity in undifferentiated HESCs exposed to ROS. Thus, JNK silencing uncouples ROS signaling from the SUMO conjugation pathway and maintains progesterone responses and cellular homeostasis in decidual cells under oxidative stress conditions imposed by pregnancy.-Leitao, B., Jones, M. C., Fusi, L., Higham, J., Lee, Y. Takano, M., Goto, T., Christian, M., Lam, E. W.-F., Brosens, J. J. Silencing of the Jnk pathway maintains progesterone receptor activity in decidualizing human endometrial stromal cells exposed to oxidative stress signals. FASEB J. 24, 1541-1551 (2010). www.fasebj.org
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available