CUL4A
Overview
CUL4A (Cullin 4A) is a scaffold protein of the CRL4 (Cullin-RING ligase 4) E3 ubiquitin ligase complex involved in DNA damage repair, replication licensing, and chromatin remodeling. CUL4A overexpression has been reported in multiple cancer types and functions oncogenically by promoting ubiquitin-mediated degradation of tumor suppressors including p21 and CDT1.
Alterations observed in the corpus
- CUL4A overexpression in osteosarcoma (OS); classified as an NAE (NEDD8-activating enzyme) inhibitor target in the PIPseq pediatric precision-oncology cohort PMID:28007021
Cancer types (linked)
- OS: CUL4A overexpression identified as an actionable alteration; neddylation inhibition (targeting the NEDD8-activating enzyme required for CRL4 activation) proposed as therapeutic approach PMID:28007021
Co-occurrence and mutual exclusivity
- Co-occurred with CCNE1, MYC, and MCL1 overexpression in the same osteosarcoma patient with multiple BET- and CDK4/6-inhibitor targets PMID:28007021
Therapeutic relevance
- NAE (NEDD8-activating enzyme) inhibitors (e.g., pevonedistat/MLN4924) proposed as a therapeutic strategy targeting CUL4A-dependent CRL4 activity in pediatric osteosarcoma PMID:28007021
Open questions
- Whether CUL4A overexpression is a driver event or a secondary consequence in osteosarcoma, and whether NAE inhibitors have clinical efficacy in CUL4A-overexpressing pediatric solid tumors, remain open questions.
Sources
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