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

Typhanie Dumontet (1) , Isabelle Sahut‐barnola (1) , Damien Dufour (1) , Anne-Marie Lefrançois-Martinez (2) , Annabel Berthon (2) , Nathanaëlle Montanier (3) , Bruno Ragazzon (4) , Cyril Djari (2) , Jean‐christophe Pointud (1) , Florence Roucher‐boulez (1) , Marie Batisse‐lignier (1, 5) , Igor Tauveron (1, 5) , Jérôme Bertherat (6, 4) , Pierre Val (1) , Antoine Martinez (1)

1 GReD - Génétique, Reproduction et Développement
2 GReD - Génétique, Reproduction et Développement
3 Service d’Endocrinologie Diabète et Maladies Métaboliques [CHU Clermont-Ferrand]
4 IC UM3 (UMR 8104 / U1016) - Institut Cochin
5 CHU Clermont-Ferrand
6 CHU Cochin [AP-HP] - Centre de référence des maladies rares de la surrénale

SUMOylation 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.

Mots clés: PIAS3.β-catenin; SENP1/2; mouse models; endocrine diseases; PKA

Domaines: Biologie moléculaire; Embryologie et organogenèse; Cancer; Génétique animale; Endocrinologie et métabolisme; Génomique, Transcriptomique et Protéomique [q-bio.GN]

Typhanie Dumontet, Isabelle Sahut‐barnola, Damien Dufour, Anne-Marie Lefrançois-Martinez, Annabel Berthon, et al.. Hormonal and spatial control of SUMOylation in the human and mouse adrenal cortex. FASEB Journal, 2019, 33 (9), pp.10218-10230. ⟨10.1096/fj.201900557R⟩. ⟨hal-03060127⟩