Cullin-associated NEDD8-disassociated protein

Function

Cullin-associated NEDD8-disassociated protein 1 (CAND1) is a protein exchange factor that accelerates the rate at which cullin1-Rbx1 equilibrates with multiple F-box proteins and thus controls the SCF ubiquitin ligase repertoire^[1]. CAND1 plays a vital role in cullin-RING E3 ligase ubiquitin proteasome systems which control protein degradation.

Disease

Relevance

In plants, silencing CAND1 expression results in dwarfing, early flowering, low seed germination percentage and delayed germination^[2]. CAND1 protects against cardiac hypertrophy and heart failure by inducing the degradation of calcineurin^[3].

CAND1 mitigates nonalcoholic fatty liver disease^[4].

Structural highlights

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3D structures of cullin-associated NEDD8-disassociated protein 1

CAND1 3D structures

Human CAND1 (yellow) complex with cullin1 (pink) and RBX1 (blue) (PDB id 7z8r)

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ReferencesReferences

↑ Pierce NW, Lee JE, Liu X, Sweredoski MJ, Graham RL, Larimore EA, Rome M, Zheng N, Clurman BE, Hess S, Shan SO, Deshaies RJ. Cand1 promotes assembly of new SCF complexes through dynamic exchange of F box proteins. Cell. 2013 Mar 28;153(1):206-15. PMID:23453757 doi:10.1016/j.cell.2013.02.024
↑ Cheng W, Yin S, Tu Y, Mei H, Wang Y, Yang Y. SlCAND1, encoding cullin-associated Nedd8-dissociated protein 1, regulates plant height, flowering time, seed germination, and root architecture in tomato. Plant Mol Biol. 2020 Mar;102(4-5):537-551. PMID:31916084 doi:10.1007/s11103-020-00963-7
↑ Li X, Zhang Y, Zhao Y, Zhou Y, Han Q, Yang Y, Zhang L, Shi L, Jin X, Zhang R, Gao H, Xue G, Li D, Zhang ZR, Lu Y, Yang B, Pan Z. Cullin-associated and neddylation-dissociated 1 protein (CAND1) governs cardiac hypertrophy and heart failure partially through regulating calcineurin degradation. Pharmacol Res. 2022 Aug;182:106284. PMID:35661710 doi:10.1016/j.phrs.2022.106284
↑ Huang X, Liu X, Li X, Zhang Y, Gao J, Yang Y, Jiang Y, Gao H, Sun C, Xuan L, Zhao L, Song J, Bao H, Zhou Z, Li S, Zhang X, Lu Y, Zhong X, Yang B, Pan Z. Cullin-associated and neddylation-dissociated protein 1 (CAND1) alleviates NAFLD by reducing ubiquitinated degradation of ACAA2. Nat Commun. 2023 Aug 1;14(1):4620. PMID:37528093 doi:10.1038/s41467-023-40327-5

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Michal Harel

[1] Pierce NW, Lee JE, Liu X, Sweredoski MJ, Graham RL, Larimore EA, Rome M, Zheng N, Clurman BE, Hess S, Shan SO, Deshaies RJ. Cand1 promotes assembly of new SCF complexes through dynamic exchange of F box proteins. Cell. 2013 Mar 28;153(1):206-15. PMID:23453757 doi:10.1016/j.cell.2013.02.024

[2] Cheng W, Yin S, Tu Y, Mei H, Wang Y, Yang Y. SlCAND1, encoding cullin-associated Nedd8-dissociated protein 1, regulates plant height, flowering time, seed germination, and root architecture in tomato. Plant Mol Biol. 2020 Mar;102(4-5):537-551. PMID:31916084 doi:10.1007/s11103-020-00963-7

[3] Li X, Zhang Y, Zhao Y, Zhou Y, Han Q, Yang Y, Zhang L, Shi L, Jin X, Zhang R, Gao H, Xue G, Li D, Zhang ZR, Lu Y, Yang B, Pan Z. Cullin-associated and neddylation-dissociated 1 protein (CAND1) governs cardiac hypertrophy and heart failure partially through regulating calcineurin degradation. Pharmacol Res. 2022 Aug;182:106284. PMID:35661710 doi:10.1016/j.phrs.2022.106284

[4] Huang X, Liu X, Li X, Zhang Y, Gao J, Yang Y, Jiang Y, Gao H, Sun C, Xuan L, Zhao L, Song J, Bao H, Zhou Z, Li S, Zhang X, Lu Y, Zhong X, Yang B, Pan Z. Cullin-associated and neddylation-dissociated protein 1 (CAND1) alleviates NAFLD by reducing ubiquitinated degradation of ACAA2. Nat Commun. 2023 Aug 1;14(1):4620. PMID:37528093 doi:10.1038/s41467-023-40327-5

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