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Cullin 4A and Cullin 4B, encoded by CUL4A and CUL4B, are scaffold proteins that assemble cullin RING E3 ubiquitin ligase complexes known as CRL4. These complexes typically pair CUL4A or CUL4B with the adaptor DDB1 and diverse DCAF substrate receptors to target numerous proteins for ubiquitination, thereby controlling DNA replication licensing through CDT1 turnover, nucleotide excision repair via regulation of DDB2 and XPC, chromatin dynamics, cell cycle progression, and signal transduction. CUL4A is frequently amplified or overexpressed in several cancers and has been linked to increased proliferation and therapy resistance, while CUL4B mutations cause an X linked intellectual disability syndrome with developmental anomalies, reflecting nonredundant functions and distinct subcellular localization patterns. CRL4 activity is regulated by NEDD8 conjugation known as neddylation, by deneddylation through the COP9 signalosome, and by availability of DCAF receptors, making the pathway sensitive to small molecule neddylation inhibitors such as MLN4924 also known as pevonedistat. Experimental interrogation of CUL4 biology includes proteomics to map DCAF interactions, ubiquitinome profiling to define substrates, and genetic perturbation to dissect isoform specific roles in genome integrity and oncogenesis.
仅用于科研。不用于诊断过程。未经明确授权不得转售。
蛋白别名: CUL-4A; CUL-4B; cullin 4A; cullin 4B; Cullin-4A; Cullin-4B; DDB1-CUL4A complex subunit; ubiquitin E3 ligase; unnamed protein product
基因别名: CUL-4B; CUL4A; CUL4B; Cullin-4A; Cullin-4B; I79_011074; I79_016255; KIAA0695; MRXHF2; MRXS15; MRXSC; RGD1563853; RGD1564494; SFM2
UniProt ID: (Human) Q13619, (Human) Q13620
Entrez Gene ID: (Human) 8451, (Human) 8450, (Rat) 361181, (Chinese hamster) 100760883, (Chinese hamster) 100763989, (Rat) 302502