Deciphering how DCAFs (DDB1-CUL4 Associated Factors) modulate a broad spectrum of cellular processes, including cell cycle progression and maintenance of genomic integrity is critical to better understand cellular homeostasis and diseases. Cells contain more than 100 DCAFs that associate with the Cullin-Ring Ubiquitin Ligase 4 (CRL4) complex that target specific protein substrates for degradation. DCAFs are thought to act as substrate receptors that dictate the specificity of the ubiquitination machinery (“catalytic DCAFs”). However, recent studies have suggested that some DCAFs might play a different role by targeting CRL4 complexes to distinct cellular compartments (“structural DCAFs”). Once localized to their correct cellular domains, these CRLs dissociate from the structural DCAFs prior to their association with other, substrate-specific catalytic DCAFs. Thus, we propose that DCAF switches can provide a mechanistic basis for the degradation of proteins that regulate cell growth and proliferation at precise points in space and time.

中文翻译：

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切换 DCAF：超越底物受体

破译 DCAF（DDB1-CUL4 相关因子）如何调节广泛的细胞过程，包括细胞周期进程和基因组完整性的维持，对于更好地了解细胞稳态和疾病至关重要。细胞包含超过 100 个 DCAF，这些 DCAF 与 Cullin-Ring 泛素连接酶 4 (CRL4) 复合物相关联，这些复合物针对特定的蛋白质底物进行降解。DCAF 被认为充当决定泛素化机制特异性的底物受体（“催化 DCAF”）。然而，最近的研究表明，一些 DCAF 可能通过将 CRL4 复合物靶向不同的细胞区室（“结构 DCAF”）而发挥不同的作用。一旦定位到其正确的细胞域，这些 CRL 在与其他结构域关联之前与结构性 DCAF 分离，底物特异性催化 DCAF。因此，我们建议 DCAF 开关可以为在精确的空间和时间点调节细胞生长和增殖的蛋白质降解提供机械基础。