Hormonal and spatial control of SUMOylation in the human and mouse adrenal cortex

• Published in: The FASEB journal 2019-09, Vol.33 (9), p.10218-10230
• Main Authors: Dumontet, Typhanie, Sahut‐Barnola, Isabelle, Dufour, Damien, Lefrançois‐Martinez, Anne‐Marie, Berthon, Annabel, Montanier, Nathanaëlle, Ragazzon, Bruno, Djari, Cyril, Pointud, Jean‐Christophe, Roucher‐Boulez, Florence, Batisse‐Lignier, Marie, Tauveron, Igor, Bertherat, Jérôme, Val, Pierre, Martinez, Antoine
• Format: Article
• Language: English
• Subjects: Adrenal Cortex; Adrenal Cortex Neoplasms; Adrenocorticotropic Hormone; Animal genetics; Animals; beta Catenin; Biochemistry, Molecular Biology; Cancer; Carney Complex; Cell Line, Tumor; Colforsin; Cyclic AMP-Dependent Protein Kinases; Cycloheximide; Dactinomycin; Delayed-Action Preparations; Development Biology; Dexamethasone; Embryology and Organogenesis; endocrine diseases; Endocrinology and metabolism; Female; Genetics; Genomics; Human health and pathology; Humans; Life Sciences; Mice; Mice, Knockout; Mice, Transgenic; Molecular biology; mouse models; Neoplasm Proteins; PIAS3.β‐catenin; PKA; Protein Processing, Post-Translational; SENP1/2; Signal Transduction; Sumoylation; Wnt Signaling Pathway; Zona Fasciculata; Zona Glomerulosa
• ISSN: 0892-6638; 1530-6860
• DOI: 10.1096/fj.201900557R

ABSTRACTSUMOylation is a highly conserved and dynamic post‐translational mechanism primarily affecting nuclear programs for adapting organisms to stressful challenges. Alteration of SUMOylation cycles leads to severe developmental and homeostatic defects and malignancy, but signals coordinating SUMOylation are still unidentified. The adrenal cortex is a zonated endocrine gland that controls body homeostasis and stress response. Here, we show that in human and in mouse adrenals, SUMOylation follows a decreasing centripetal gradient that mirrors cortical differentiation flow and delimits highly and weakly SUMOylated steroidogenic compartments, overlapping glomerulosa, and fasciculata zones. Activation of PKA signaling by acute hormonal treatment, mouse genetic engineering, or in Carney complex results in repression of small ubiquitin‐like modifier (SUMO) conjugation in the inner cortex by coordinating expression of SUMO pathway inducers and repressors. Conversely, genetic activation of canonical wingless‐related integration site signaling maintains high SUMOylation potential in the outer neoplastic cortex. Thus, SUMOylation is tightly regulated by signaling pathways that orchestrate adrenal zonation and diseases.—Dumontet, T., Sahut‐Barnola, I., Dufour, D., Lefrançois‐Martinez, A.‐M., Berthon, A., Montanier, N., Ragazzon, B., Djari, C., Pointud, J.‐C., Roucher‐Boulez, F., Batisse‐Lignier, M., Tauveron, I., Bertherat, J., Val, P., Martinez, A. Hormonal and spatial control of SUMOylation in the human and mouse adrenal cortex. FASEB J. 33, 10218–10230 (2019). www.fasebj.org