MassIVE MSV000095414

Complete Public PXD054138

Autophosphorylation of conserved yeast and human casein kinase 1 isozymes regulates Elongator dependent tRNA modifications

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Description

Casein kinase 1 (CK1) family members are crucial for ER-Golgi trafficking, calcium signaling, DNA repair, tRNA modifications and circadian rhythmicity. Whether and how substrate interactions and kinase autophosphorylation contribute to these diverse cellular processes and CK1 plasticity remains largely unknown. Here, we undertake a comprehensive phylogenetic, cellular and molecular characterization of Hrr25 from budding yeast and identify isozyme CK1 epsilon as its human ortholog. We analyze the effect of Hrr25 depletion and catalytically inactive mutants in vivo and show that perturbations in CK1 activity lead to pleiotropic stress-induced growth defects, morphological abnormalities and loss of Elongator-dependent tRNA modification. We use purified Hrr25 protein to identify distinct autophosphorylation patterns and phospho-sites on several physiological substrates in vitro and find that only human isozyme CK1epsilon can replace yeast Hrr25 functions essential for tRNA modification and cell proliferation in vivo. Furthermore, we demonstrate that human and yeast CK1 orthologs share conserved autophosphorylation sites, which regulate their activities and mutually exclusive interactions with Sit4, a phosphatase antagonist of Hrr25, and Elongator subunit Elp1. Thus, autophosphorylation controls CK1 activity and regulates the tRNA modification pathway. Our data offer mechanistic insights into regulatory roles of CK1 that are conserved from yeast to human cells and reveal a complex phosphorylation network behind CK1 plasticity. [doi:10.25345/C5QB9VH6V] [dataset license: CC0 1.0 Universal (CC0 1.0)]

Keywords: yeast Hrr25 ; kinase 39 autophosphorylation ; Elongator complex ; Casein kinase 1 epsilon

Contact

Principal Investigators:
(in alphabetical order) 		Raffael Schaffrath, Institute of Biology, Department of Microbiology, University of Kassel, Germany
Sebastian Glatt, Malopolska Centre of Biotechnology (MCB), Jagiellonian University, Poland
Submitting User: Urszula

Publications

Landrock MF, Krutyho?owa R, Böhnert P, Mazur J, Honc M, Hammermeister A, Bessler L, Scherf D, Elms A, Radczuk N, Skupien-Rabian B, Jankowska U, Herberg FW, Helm M, Klassen R, Glatt S, Schaffrath R.
Autophosphorylation of conserved yeast and human casein kinase 1 isozymes regulates Elongator-dependent tRNA modifications.
Nucleic Acids Res.

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