CK1‐mediated phosphorylation of FAM110A promotes its interaction with mitotic spindle and controls chromosomal alignment

Perez, Cecilia Aquino; Burócziová, Monika; Jeníková, Gabriela; Macůrek, Libor

doi:10.15252/embr.202051847

Cited by 6 publications

(1 citation statement)

References 87 publications

(109 reference statements)

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“…In this study, it was demonstrated that CK1 interacts with FAM110A during mitosis, and inhibition of CK1 or depletion of FAM110A, led to chromosomal alignment defects and delayed mitosis progression ( Figure 3 ). Interestingly, defects in chromosomal alignment were rescued by mimicking phosphorylation with FAM110A-S252-255E mutants [ 68 ]. Functional binding partners of CK1, such as the anchoring proteins FAM83 and FAM110A, could be used as alternative targets in cancer treatment by blocking specifically the interaction of CK1 isoforms with these anchoring proteins and thus, inhibiting CK1 isoform-mediated substrate phosphorylation (see also Section 7.4 ) [ 68 ].…”

Section: The Role Of Ck1 In Cell Cycle Progressionmentioning

confidence: 99%

CK1 Is a Druggable Regulator of Microtubule Dynamics and Microtubule-Associated Processes

Roth

Gihring

Bischof

et al. 2022

Cancers

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Protein kinases of the Casein Kinase 1 family play a vital role in the regulation of numerous cellular processes. Apart from functions associated with regulation of proliferation, differentiation, or apoptosis, localization of several Casein Kinase 1 isoforms to the centrosome and microtubule asters also implicates regulatory functions in microtubule dynamic processes. Being localized to the spindle apparatus during mitosis Casein Kinase 1 directly modulates microtubule dynamics by phosphorylation of tubulin isoforms. Additionally, site-specific phosphorylation of microtubule-associated proteins can be related to the maintenance of genomic stability but also microtubule stabilization/destabilization, e.g., by hyper-phosphorylation of microtubule-associated protein 1A and RITA1. Consequently, approaches interfering with Casein Kinase 1-mediated microtubule-specific functions might be exploited as therapeutic strategies for the treatment of cancer. Currently pursued strategies include the development of Casein Kinase 1 isoform-specific small molecule inhibitors and therapeutically useful peptides specifically inhibiting kinase-substrate interactions.

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Section: The Role Of Ck1 In Cell Cycle Progressionmentioning

confidence: 99%

CK1 Is a Druggable Regulator of Microtubule Dynamics and Microtubule-Associated Processes

Roth

Gihring

Bischof

et al. 2022

Cancers

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Mitotic spindle formation in the absence of Polo kinase

Kim

Goshima

2022

Proc. Natl. Acad. Sci. U.S.A.

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Significance Mitosis is an essential process in all eukaryotes, but paradoxically, genes required for mitosis vary among species. The essentiality of many mitotic genes was bypassed by activating alternative mechanisms during evolution. However, bypass events have rarely been recapitulated experimentally. Here, using the fission yeast Schizosaccharomyces pombe , the essentiality of a kinase (Plo1) required for bipolar spindle formation was bypassed by other mutations, many of which are associated with glucose metabolism. The Plo1 bypass by the reduction in glucose uptake was dependent on another kinase (casein kinase I), which potentiated spindle microtubule formation. This study illustrates a rare experimental bypass of essentiality for mitotic genes and provides insights into the molecular diversity of mitosis.

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Mitotic spindle formation in the absence of Polo kinase

Kim

Goshima

2021

Preprint

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Mitosis is a fundamental process in every eukaryote, in which chromosomes are segregated into two daughter cells by the action of the microtubule (MT)-based spindle. Despite this common principle, genes essential for mitosis are variable among organisms. This indicates that the loss of essential genes or bypass-of-essentiality (BOE) occurred multiple times during evolution. While many BOE relationships have been recently revealed experimentally, the BOE of mitosis regulators (BOE-M) has been scarcely reported and how this occurs remains largely unknown. Here, by mutagenesis and subsequent evolutionary repair experiments, we isolated viable fission yeast strains that lacked the entire coding region of Polo-like kinase (Plk), a versatile essential mitotic kinase. The BOE of Plk was enabled by specific mutations in the downstream machinery, including the MT-nucleating γ-tubulin complex, and more surprisingly, through downregulation of glucose uptake, which is not readily connected to mitosis. The latter bypass was dependent on casein kinase I (CK1), which has not been considered as a major mitotic regulator. Our genetic and phenotypic data suggest that CK1 constitutes an alternative mechanism of MT nucleation, which is normally dominated by Plk. A similar relationship was observed in a human colon cancer cell line. Thus, our study shows that BOE-M can be achieved by simple genetic or environmental changes, consistent with the occurrence of BOE-M during evolution. Furthermore, the identification of BOE-M constitutes a powerful means to uncover a hitherto under-studied mechanism driving mitosis and also hints at the limitations and solutions for selecting chemotherapeutic compounds targeting mitosis.

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CK1‐mediated phosphorylation of FAM110A promotes its interaction with mitotic spindle and controls chromosomal alignment

Cited by 6 publications

References 87 publications

CK1 Is a Druggable Regulator of Microtubule Dynamics and Microtubule-Associated Processes

CK1 Is a Druggable Regulator of Microtubule Dynamics and Microtubule-Associated Processes

Mitotic spindle formation in the absence of Polo kinase

Mitotic spindle formation in the absence of Polo kinase

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