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Updated: Jan 23, 2026
In Vivo Detection and Analysis of Rb Protein SUMOylation in Human Cells
Published on: November 2, 2017
Hormonal and spatial control of SUMOylation in the human and mouse adrenal cortex
Typhanie Dumontet1, Isabelle Sahut-Barnola1, Damien Dufour1
1Génétique Reproduction and Dévelopement (GReD), Centre National de la Recherche Scientifique (CNRS), INSERM, Université Clermont-Auvergne, Clermont-Ferrand, France.
Abstract:
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.-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.
Insights
SUMOylation, a key protein modification, follows a specific gradient in the adrenal cortex, influencing cell differentiation and stress response. Signaling pathways like PKA and Wnt regulate this process, impacting adrenal health and disease.
Area of Science:
- Endocrinology
- Molecular Biology
- Cellular Biology
Background:
- SUMOylation is a crucial post-translational modification regulating nuclear functions and cellular adaptation to stress.
- Dysregulated SUMOylation is linked to developmental issues, homeostatic imbalances, and cancer.
- The adrenal cortex, a zonation-dependent endocrine gland, plays a vital role in homeostasis and stress response, but the signals controlling its SUMOylation remain unclear.
Purpose of the Study:
- To investigate the spatial distribution and regulation of SUMOylation within the human and mouse adrenal cortex.
- To identify signaling pathways that coordinate SUMOylation gradients and their role in adrenal zonation and disease.
Main Methods:
- Analysis of SUMOylation levels across different zones of the human and mouse adrenal cortex.
- Investigated the impact of PKA and Wnt signaling pathways on SUMOylation.
- Utilized hormonal treatments and genetic engineering in mouse models.
- Examined SUMOylation in the context of Carney complex and neoplastic adrenal tissue.
Main Results:
- SUMOylation exhibits a decreasing centripetal gradient in the adrenal cortex, correlating with differentiation.
- Highly and weakly SUMOylated compartments align with the glomerulosa and fasciculata zones, respectively.
- Activation of PKA signaling represses SUMOylation in the inner cortex by modulating SUMO pathway components.
- Canonical Wnt signaling activation maintains high SUMOylation in the outer neoplastic cortex.
Conclusions:
- SUMOylation is spatially regulated within the adrenal cortex, following a gradient that mirrors cellular differentiation.
- PKA and Wnt signaling pathways are key regulators of SUMOylation in the adrenal cortex, influencing zonation and disease development.
- Understanding these regulatory mechanisms is crucial for addressing adrenal disorders associated with SUMOylation defects.
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