CDK1 couples proliferation with protein synthesis

Katharina Haneke; Johanna Schott; Doris Lindner; Anne Kruse Hollensen; Christian Kroun Damgaard; Cyril Mongis; Michael Knop; Wilhelm Palm; Alessia Ruggieri; Georg Stoecklin

doi:10.1083/jcb.201906147

CDK1 couples proliferation with protein synthesis

Katharina Haneke, Johanna Schott, Doris Lindner, Anne Kruse Hollensen, Christian Kroun Damgaard, Cyril Mongis, Michael Knop, Wilhelm Palm, Alessia Ruggieri, Georg Stoecklin

Institut for Molekylærbiologi og Genetik - RNA-biologi og -innovation

Publikation: Bidrag til tidsskrift/Konferencebidrag i tidsskrift /Bidrag til avis › Tidsskriftartikel › Forskning › peer review

71 Citationer (Scopus)

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Abstract

Cell proliferation exerts a high demand on protein synthesis, yet the mechanisms coupling the two processes are not fully understood. A kinase and phosphatase screen for activators of translation, based on the formation of stress granules in human cells, revealed cell cycle-associated kinases as major candidates. CDK1 was identified as a positive regulator of global translation, and cell synchronization experiments showed that this is an extramitotic function of CDK1. Different pathways including eIF2α, 4EBP, and S6K1 signaling contribute to controlling global translation downstream of CDK1. Moreover, Ribo-Seq analysis uncovered that CDK1 exerts a particularly strong effect on the translation of 5'TOP mRNAs, which includes mRNAs encoding ribosomal proteins and several translation factors. This effect requires the 5'TOP mRNA-binding protein LARP1, concurrent to our finding that LARP1 phosphorylation is strongly dependent on CDK1. Thus, CDK1 provides a direct means to couple cell proliferation with biosynthesis of the translation machinery and the rate of protein synthesis.

Originalsprog	Engelsk
Artikelnummer	e201906147
Tidsskrift	The Journal of Cell Biology
Vol/bind	219
Nummer	3
Antal sider	23
ISSN	0021-9525
DOI	https://doi.org/10.1083/jcb.201906147
Status	Udgivet - 2020

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10.1083/jcb.201906147Licens: CC BY

jcb_201906147Forlagets udgivne version, 6,24 MBLicens: CC BY

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Citationsformater

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title = "CDK1 couples proliferation with protein synthesis",

abstract = "Cell proliferation exerts a high demand on protein synthesis, yet the mechanisms coupling the two processes are not fully understood. A kinase and phosphatase screen for activators of translation, based on the formation of stress granules in human cells, revealed cell cycle-associated kinases as major candidates. CDK1 was identified as a positive regulator of global translation, and cell synchronization experiments showed that this is an extramitotic function of CDK1. Different pathways including eIF2α, 4EBP, and S6K1 signaling contribute to controlling global translation downstream of CDK1. Moreover, Ribo-Seq analysis uncovered that CDK1 exerts a particularly strong effect on the translation of 5'TOP mRNAs, which includes mRNAs encoding ribosomal proteins and several translation factors. This effect requires the 5'TOP mRNA-binding protein LARP1, concurrent to our finding that LARP1 phosphorylation is strongly dependent on CDK1. Thus, CDK1 provides a direct means to couple cell proliferation with biosynthesis of the translation machinery and the rate of protein synthesis.",

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T1 - CDK1 couples proliferation with protein synthesis

AU - Haneke, Katharina

AU - Schott, Johanna

AU - Lindner, Doris

AU - Hollensen, Anne Kruse

AU - Damgaard, Christian Kroun

AU - Mongis, Cyril

AU - Knop, Michael

AU - Palm, Wilhelm

AU - Ruggieri, Alessia

AU - Stoecklin, Georg

PY - 2020

Y1 - 2020

N2 - Cell proliferation exerts a high demand on protein synthesis, yet the mechanisms coupling the two processes are not fully understood. A kinase and phosphatase screen for activators of translation, based on the formation of stress granules in human cells, revealed cell cycle-associated kinases as major candidates. CDK1 was identified as a positive regulator of global translation, and cell synchronization experiments showed that this is an extramitotic function of CDK1. Different pathways including eIF2α, 4EBP, and S6K1 signaling contribute to controlling global translation downstream of CDK1. Moreover, Ribo-Seq analysis uncovered that CDK1 exerts a particularly strong effect on the translation of 5'TOP mRNAs, which includes mRNAs encoding ribosomal proteins and several translation factors. This effect requires the 5'TOP mRNA-binding protein LARP1, concurrent to our finding that LARP1 phosphorylation is strongly dependent on CDK1. Thus, CDK1 provides a direct means to couple cell proliferation with biosynthesis of the translation machinery and the rate of protein synthesis.

AB - Cell proliferation exerts a high demand on protein synthesis, yet the mechanisms coupling the two processes are not fully understood. A kinase and phosphatase screen for activators of translation, based on the formation of stress granules in human cells, revealed cell cycle-associated kinases as major candidates. CDK1 was identified as a positive regulator of global translation, and cell synchronization experiments showed that this is an extramitotic function of CDK1. Different pathways including eIF2α, 4EBP, and S6K1 signaling contribute to controlling global translation downstream of CDK1. Moreover, Ribo-Seq analysis uncovered that CDK1 exerts a particularly strong effect on the translation of 5'TOP mRNAs, which includes mRNAs encoding ribosomal proteins and several translation factors. This effect requires the 5'TOP mRNA-binding protein LARP1, concurrent to our finding that LARP1 phosphorylation is strongly dependent on CDK1. Thus, CDK1 provides a direct means to couple cell proliferation with biosynthesis of the translation machinery and the rate of protein synthesis.

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U2 - 10.1083/jcb.201906147

DO - 10.1083/jcb.201906147

M3 - Journal article

C2 - 32040547

SN - 0021-9525

VL - 219

JO - The Journal of Cell Biology

JF - The Journal of Cell Biology

IS - 3

M1 - e201906147

ER -

CDK1 couples proliferation with protein synthesis

Abstract

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