Proteopedia

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. Cullin-associated NEDD8-disassociated protein 2 (CAND2) is linked to mTOR singnaling[2].

Disease

Relevance

In plants, silencing CAND1 expression results in dwarfing, early flowering, low seed germination percentage and delayed germination[3]. CAND1 protects against cardiac hypertrophy and heart failure by inducing the degradation of calcineurin[4].

CAND1 mitigates nonalcoholic fatty liver disease[5].

Structural highlights

The 3D structure of the complex between CAND1, cullin1 and RBX as well as other 3D structures of the SCF ubiquitin E3 ligases provide a mechanism of multiprotein complex assembly that averts supply chain problems and rapidly establishes protein degradation pathways needed for cellular regulation[6].

3D structures of cullin-associated NEDD8-disassociated protein

CAND1 3D structures


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

Drag the structure with the mouse to rotate

ReferencesReferences

  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. ↑ Górska AA, Sandmann C, Riechert E, Hofmann C, Malovrh E, Varma E, Kmietczyk V, Ölschläger J, Jürgensen L, Kamuf-Schenk V, Stroh C, Furkel J, Konstandin MH, Sticht C, Boileau E, Dieterich C, Frey N, Katus HA, Doroudgar S, Völkers M. Muscle-specific Cand2 is translationally upregulated by mTORC1 and promotes adverse cardiac remodeling. EMBO Rep. 2021 Dec 6;22(12):e52170. PMID:34605609 doi:10.15252/embr.202052170
  3. ↑ 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
  4. ↑ 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
  5. ↑ 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
  6. ↑ Baek K, Scott DC, Henneberg LT, King MT, Mann M, Schulman BA. Systemwide disassembly and assembly of SCF ubiquitin ligase complexes. Cell. 2023 Mar 31:S0092-8674(23)00213-1. PMID:37028429 doi:10.1016/j.cell.2023.02.035

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Michal Harel
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