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Wyszukujesz frazę "Scherf, David" wg kryterium: Autor


Wyświetlanie 1-4 z 4
Tytuł:
tRNA binding to Kti12 is crucial for wobble uridine modification by Elongator
Autorzy:
Burkard, Alicia
Helm, Mark
Scherf, David
Schaffrath, Raffael
Hammermeister, Alexander
Böhnert, Pauline
Glatt, Sebastian
Opis:
In yeast, tRNA modifications that are introduced by the Elongator complex are recognized by zymocin, a fungal tRNase killer toxin that cleaves the anticodon. Based on zymocin resistance conferred by mutations in KTI12, a gene coding for an Elongator interactor, we further examined the yet vaguely defined cellular role of Kti12. Guided by structural similarities between Kti12 and PSTK, a tRNA kinase involved in selenocysteine synthesis, we identified conserved basic residues in the C-terminus of Kti12, which upon site-directed mutagenesis caused progressive loss of tRNA binding in vitro. The inability of Kti12 to bind tRNA led to similar phenotypes caused by Elongator inactivation in vivo. Consistently, tRNA binding deficient kti12 mutants drastically suppressed Elongator dependent tRNA anticodon modifications and reduced the capacity of Kti12 to interact with Elongator. We further could distinguish Elongator unbound pools of Kti12 in a tRNA dependent manner from bound ones. In summary, the C-terminal domain of Kti12 is crucial for tRNA binding and Kti12 recruitment to Elongator, which are both requirements for Elongator function suggesting Kti12 is a tRNA carrier that interacts with Elongator for modification of the tRNA anticodon.
Dostawca treści:
Repozytorium Uniwersytetu Jagiellońskiego
Artykuł
Tytuł:
Autophosphorylation of conserved yeast and human casein kinase 1 isozymes regulates Elongator-dependent tRNA modifications
Autorzy:
Landrock, Maria Friederike
Böhnert, Pauline
Scherf, David
Schaffrath, Raffael
Honc, Małgorzata
Jankowska, Urszula
Hammermeister, Alexander
Bessler, Larissa
Klassen, Roland
Herberg, Friedrich W
Glatt, Sebastian
Radczuk, Natalia
Mazur, Jarosław
Skupień-Rabian, Bożena
Elms, Anna
Krutyhołowa, Rościsław
Helm, Mark
Opis:
Casein kinase 1 (CK1) family members are crucial for ER-Golgi trafficking, calcium signalling, DNA repair, transfer RNA (tRNA) modifications, and circadian rhythmicity. Whether and how substrate interactions and kinase autophosphorylation contribute to CK1 plasticity remains largely unknown. Here, we undertake a comprehensive phylogenetic, cellular, and molecular characterization of budding yeast CK1 Hrr25 and identify human CK1 epsilon (CK1ϵ) as its ortholog. We analyse the effect of Hrr25 depletion and catalytically inactive mutants in vivo and show that perturbations in CK1 activity lead to 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 only human isozyme CK1ϵ 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 within the kinase domains, which regulate their activities and mutually exclusive interactions with Elongator subunit Elp1 and Sit4, a phosphatase antagonist of Hrr25. Thus, autophosphorylation controls CK1 activity and regulates the tRNA modification pathway. Our data offer mechanistic insights into regulatory roles of CK1 that are conserved between yeast and human cells and reveal a complex phosphorylation network behind CK1 plasticity.
Dostawca treści:
Repozytorium Uniwersytetu Jagiellońskiego
Artykuł
    Wyświetlanie 1-4 z 4

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