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Badarudeen, Binshad; Anand, Ushma; Mukhopadhyay, Swarnendu; Manna, Tapas K.
The FEBS journal, August 2022, 2022-08-00, 20220801, Volume: 289, Issue: 16Journal Article
The centrosome plays an essential role in maintaining genetic stability, ciliogenesis and cell polarisation. The core of the centrosome is made up of two centrioles that duplicate precisely once during every cell cycle to generate two centrosomes that are required for bipolar spindle assembly and chromosome segregation. Abundance of centriole proteins at optimal levels and their recruitment to the centrosome are tightly regulated in time and space in order to restrict aberrant duplication of centrioles, a phenomenon that is observed in many cancers. Recent advances have conclusively shown that dedicated ubiquitin ligase‐dependent protein degradation machineries are involved in governing centriole duplication. These studies revealed intricate mechanistic insights into how the ubiquitin ligases target different centriole proteins. In certain cases, a specific ubiquitin ligase targets a number of substrate proteins that co‐regulate centriole assembly, prompting the possibility that substrate‐targeting occurs during formation of the sub‐centriolar structures. There are also instances where a specific centriole duplication protein is targeted by several ubiquitin ligases at different stages of the cell cycle, suggesting synchronised actions. Recent evidence also indicated a direct association of E3 ubiquitin ligase with the centrioles, supporting the notion that substrate‐targeting occurs in the organelle itself. In this review, we highlight these advances by underlining the mechanisms of how different ubiquitin ligase machineries control centriole duplication and discuss our views on their coordination. Correct duplication of centrioles is crucial for chromosomal stability and cell polarisation. Centriole over‐duplication is controlled via ubiquitin ligase‐mediated degradation of key centriole duplication proteins. While during mitosis and G1, APC/C‐Cdh1 targets STIL, SAS‐6 and CPAP for degradation; these proteins as well as Plk4 and CP110 are targeted by specific SCF‐ubiquitin ligases during S and G2. This review focuses on the molecular mechanisms of various ubiquitin ligases regulating centriole duplication.
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