DDB1- and CUL4-associated factor 12

Definition:

Substrate-recognition component of a DCX (DDB1-CUL4-X-box) E3 ubiquitin-protein ligase complex of the DesCEND (destruction via C-end degrons) pathway, which recognizes a C-degron located at the extreme C terminus of target proteins, leading to their ubiquitination and degradation. The C-degron recognized by the DesCEND pathway is usually a motif of less than ten residues and can be present in full-length proteins, truncated proteins or proteolytically cleaved forms. The DCX(DCAF12) complex specifically recognizes proteins with a diglutamate (Glu-Glu) at the C-terminus, such as MAGEA3, MAGEA6 and CCT5, leading to their ubiquitination and degradation. Ubiquitination of MAGEA3, MAGEA6 by DCX(DCAF12) complex is required for starvation-induced autophagy.

References:

[1]. Stephane Angers, et al. Molecular architecture and assembly of the DDB1-CUL4A ubiquitin ligase machinery. Nature. 2006 Oct 5;443(7111):590-3. [Content Brief]

[2]. Itay Koren, et al. The Eukaryotic Proteome Is Shaped by E3 Ubiquitin Ligases Targeting C-Terminal Degrons. Cell. 2018 Jun 14;173(7):1622-1635.e14. [Content Brief]

[3]. Ramya Ravichandran, et al. Regulation of MAGE-A3/6 by the CRL4-DCAF12 ubiquitin ligase and nutrient availability. EMBO Rep. 2019 Jul;20(7):e47352. [Content Brief]

[4]. Jianping Jin, et al. A family of diverse Cul4-Ddb1-interacting proteins includes Cdt2, which is required for S phase destruction of the replication factor Cdt1. Mol Cell. 2006 Sep 1;23(5):709-21. [Content Brief]

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