title: Modifications to glucocorticoid and progesterone receptors alter cell fate in breast cancer.
abstract: Steroid hormone receptors (SRs) are heavily posttranslationally modified by the reversible addition of a variety of molecular moieties, including phosphorylation, acetylation, methylation, SUMOylation, and ubiquitination. These rapid and dynamic modifications may be combinatorial and interact (i.e. may be sequential, complement, or oppose each other), creating a vast array of uniquely modified receptor subspecies that allow for diverse receptor behaviors that enable highly sensitive and context-dependent hormone action. For example, in response to hormone or growth factor membrane-initiated signaling events, posttranslational modifications (PTMs) to SRs alter protein-protein interactions that govern the complex process of promoter or gene-set selection coupled to transcriptional repression or activation. Unique phosphorylation events allow SRs to associate or disassociate with specific cofactors that may include pioneer factors and other tethering partners, which specify the resulting transcriptome and ultimately change cell fate. The impact of PTMs on SR action is particularly profound in the context of breast tumorigenesis, in which frequent alterations in growth factor-initiated signaling pathways occur early and act as drivers of breast cancer progression toward endocrine resistance. In this article, with primary focus on breast cancer relevance, we review the mechanisms by which PTMs, including reversible phosphorylation events, regulate the closely related SRs, glucocorticoid receptor and progesterone receptor, allowing for precise biological responses to ever-changing hormonal stimuli.
authors.affiliation: Department of Medicine and Pharmacology University of Minnesota Twin Cities MinneapolisMinnesota, USA.
authors.forename: Katherine A
authors.initials: KA
authors.lastname: Leehy
authors.affiliation: Department of Medicine and Pharmacology University of Minnesota Twin Cities MinneapolisMinnesota, USA.
authors.forename: Tarah M
authors.initials: TM
authors.lastname: Regan Anderson
authors.affiliation: Department of Medicine and Pharmacology University of Minnesota Twin Cities MinneapolisMinnesota, USA.
authors.forename: Andrea R
authors.initials: AR
authors.lastname: Daniel
authors.affiliation: Department of Medicine and Pharmacology University of Minnesota Twin Cities MinneapolisMinnesota, USA lange047@umn.edu.
authors.forename: Carol A
authors.initials: CA
authors.lastname: Lange
authors.affiliation: Department of Medicine and Pharmacology University of Minnesota Twin Cities MinneapolisMinnesota, USA.
authors.forename: Julie H
authors.initials: JH
authors.lastname: Ostrander
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D005260:Female; D015870:Gene Expression; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D011379:Prognosis; D020033:Protein Isoforms; D011499:Protein Processing, Post-Translational; D011960:Receptors, Estrogen / Q000378:metabolism; D011965:Receptors, Glucocorticoid / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011980:Receptors, Progesterone / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D013312:Stress, Physiological; D013329:Structure-Activity Relationship
chemical_list: D020033:Protein Isoforms; D011960:Receptors, Estrogen; D011965:Receptors, Glucocorticoid; D011980:Receptors, Progesterone
keywords: breast cancer; glucocorticoid receptor; phosphorylation; posttranslational modification; progesterone receptor; protein kinases; signal transduction; steroid hormones
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