Centrosome plays essential roles in maintaining genetic stability, ciliogenesis and cell polarization. The core of centrosome is made 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 evidenced 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 synchronized 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 how different ubiquitin ligase machineries control centriole duplication and discuss our views on their coordination. This article is protected by copyright. All rights reserved tumorigenesis and also certain developmental diseases such as, microcephaly [1][2][3][4][5]. Supernumerary centrioles/centrosomes are hallmarks of many cancer cells and promote cancer transformation [6]. Structurefunction aberration of centrosomes/centrioles is also known as the causal factor of various ciliary dysfunctions (ciliopathies), and male infertility. Centriole, in a specially matured form, the basal body, serves as the platform for cilia and flagella assembly [7]. During the G1 to S phase entry of the cell cycle, each mother centriole of centrosome initiates assembly of a daughter centriole at its proximal end, which further elongates to a size precisely up to that of the mother centriole during the S till G2 phase. After the new centrioles attain the optimal size and maturation, the older (mother) centrioles are disengaged from each other and thereby, the duplicated centrosomes each consisting the pair of the old and the new centriole are produced [8]. Centriole duplication in somatic cells is extremely accurate such that only one daughter centriole is formed from the mother and the mother duplicates strictly once during the cell cycle. The mechanisms how the daughter centriole is generated from the pre-existing mother centriole and how cells restrict centriole reduplication or over-duplication by limiting formation of a single daughter centriole per mother ce...
Gamma-tubulin ring complex (γ-TuRC), composed of γ-tubulin and multiple γ-tubulin complex proteins (GCPs), serve as the major microtubule nucleating complex in animal cells. However, several γ-TuRC-associated proteins have been shown to control its function. Centrosomal adaptor protein, TACC3, is one such γ-TuRC-interacting factor that is essential for proper mitotic spindle assembly across organisms. ch-TOG is another microtubule assembly-promoting protein, which interacts with TACC3 and cooperates in mitotic spindle assembly. However, the mechanism how TACC3-ch-TOG interaction regulates microtubule assembly and the γ-TuRC functions at the centrosomes remain unclear. Here, we show that deletion of the ch-TOG-binding region in TACC3 enhances recruitment of the γ-TuRC proteins to centrosomes and aggravates spindle microtubule assembly in human cells. Loss of TACC3-ch-TOG binding imparts stabilization on TACC3 interaction with the γ-TuRC proteins and it does so by stimulating TACC3 phosphorylation and thereby enhancing phospho-TACC3 recruitment to the centrosomes. We also show that localization of ch-TOG at the centrosomes is substantially reduced and the same on the spindle microtubules is increased in its TACC3-unbound condition. Additional results reveal that ch-TOG depletion stimulates γ-tubulin localization on the spindles without significantly affecting the centrosomal γ-tubulin level. The results indicate that ch-TOG binding to TACC3 controls TACC3 phosphorylation and TACC3-mediated stabilization of the γ-TuRCs at the centrosomes. They also implicate that the spatio-temporal control of TACC3 phosphorylation via ch-TOG-binding ensures mitotic spindle assembly to the optimal level.
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