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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

CuIlin 3 targets the tumor suppressor gene ARMC5 for ubiquitination and degradation

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Cavalcante, Isadora Pontes [1] ; Vaczlavik, Anna [1] ; Drougat, Ludivine [1] ; Pacicco Lotfi, Claudimara Ferini [2] ; Hecale-Perlemoine, Karine [1] ; Ribes, Christopher [1] ; Rizk-Rabin, Marthe [1] ; Clauser, Eric [3] ; Barisson Villares Fragoso, Maria Candida [4] ; Bertherat, Jerome [1, 5] ; Ragazzon, Bruno [1]
Total Authors: 11
[1] Univ Paris, Inst Cochin, CNRS, INSERM, Paris - France
[2] Univ Sao Paulo, Inst Biomed Sci, Dept Anat, Sao Paulo - Brazil
[3] Univ Paris, INSERM, PARCC, Paris - France
[4] Univ Sao Paulo, Hosp Clin, Sch Med, Adrenal Unit, Hormone & Mol Genet Lab LIM42, Sao Paulo - Brazil
[5] Cochin Hosp, AP HP, Dept Endocrinol, Paris - France
Total Affiliations: 5
Document type: Journal article
Source: Endocrine-Related Cancer; v. 27, n. 4, p. 221-230, APR 2020.
Web of Science Citations: 0

ARMC5 (Armadillo repeat containing 5 gene) was identified as a new tumor suppressor gene responsible for hereditary adrenocortical tumors and meningiomas. ARMC5 is ubiquitously expressed and encodes a protein which contains a N-terminal Armadillo repeat domain and a C-terminal BTB (Bric-a-Brac, Tramtrack and Broad-complex) domain, both docking platforms for numerous proteins. At present, expression regulation and mechanisms of action of ARMC5 are almost unknown. In this study, we showed that ARMC5 interacts with CUL3 requiring its BTB domain. This interaction leads to ARMC5 ubiquitination and further degradation by the proteasome. ARMC5 alters cell cycle (G1/S phases and cyclin E accumulation) and this effect is blocked by CUL3. Moreover, missense mutants in the BTB domain of ARMC5, identified in patients with multiple adrenocortical tumors, are neither able to interact and be degraded by CUL3/proteasome nor alter cell cycle. These data show a new mechanism of regulation of the ARMC5 protein and open new perspectives in the understanding of its tumor suppressor activity. (AU)

FAPESP's process: 15/50192-9 - Advances in the understanding of the pathophysiology of primary adrenocortical hyperplasia macronodular - PMAH (GP-PMAH)
Grantee:Maria Candida Barisson Villares Fragoso
Support type: Research Projects - Thematic Grants