CUL5-mediated ubiquitination in cancer cell therapy: context-dependent roles, molecular networks, and emerging...

Area of Science:

• Oncology
• Molecular Biology
• Cancer Therapeutics

Background:

• Cullin-RING ligase 5 (CUL5) is a core scaffold protein regulating protein stability via the ubiquitin-proteasome system (UPS).
• CUL5 plays a critical role in cancer initiation, progression, and cellular therapy.
• Its activity is dependent on NEDD8-mediated neddylation.

Purpose of the Study:

• To systematically review the context-dependent role of CUL5 in cancer.
• To elucidate the molecular regulatory network of CUL5-mediated ubiquitination.
• To explore the therapeutic targeting potential of CUL5 in cancer cell therapy.

Main Methods:

• Literature review focusing on CUL5's role in cancer.
• Analysis of CUL5's impact on signaling pathways (e.g., NOXA, mTORC, TRAF6/NF-κB, JAK/STAT).
• Examination of CUL5's function in adoptive cell therapies (CAR-T, TCR-T, CAR-NK).

Main Results:

• CUL5 dysregulation affects tumor proliferation, apoptosis, metabolism, angiogenesis, and the immune microenvironment.
• CUL5 exhibits dual regulatory functions with varying prognostic correlations across cancer types.
• Inhibitors and nano-delivery systems targeting CUL5 present novel therapeutic strategies.
• Modulating CUL5 enhances immune cell proliferation, cytokine secretion, and anti-tumor efficacy in adoptive cell therapies.

Conclusions:

• CUL5 is a multidimensional player in tumor cell therapy.
• CUL5 holds significant potential as a therapeutic target in combined and precision medicine approaches.
• Targeting CUL5 can improve the efficacy of adoptive cell therapies.