The structure and substrate specificity of human Cdk12/Cyclin K

J 2014

The structure and substrate specificity of human Cdk12/Cyclin K

BÖSKEN, Christian A.; Lucas FARNUNG; Corinna HINTERMAIR; Miriam Merzel SCHACHTER; Karin VOGEL- BACHMAYR et al.

Základní údaje

Originální název

The structure and substrate specificity of human Cdk12/Cyclin K

Autoři

BÖSKEN, Christian A.; Lucas FARNUNG; Corinna HINTERMAIR; Miriam Merzel SCHACHTER; Karin VOGEL- BACHMAYR; Dalibor BLAŽEK; Kanchan ANAND; Robert P. FISHER; Dirk EICK a Matthias GEYER

Vydání

NATURE COMMUNICATIONS, London, Nature Publishing Group, 2014, 2041-1723

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

10600 1.6 Biological sciences

Stát vydavatele

Velká Británie a Severní Irsko

Utajení

není předmětem státního či obchodního tajemství

Odkazy

URL

Impakt faktor

Impact factor: 11.470

Označené pro přenos do RIV

Ano

Kód RIV

RIV/00216224:14740/14:00073691

Organizační jednotka

Středoevropský technologický institut

Klíčová slova anglicky

RNA-POLYMERASE-II; C-TERMINAL DOMAIN; CAPPING ENZYME RECRUITMENT; CYCLIN-DEPENDENT KINASE-9; CTD CODE; P-TEFB; PROTEIN-KINASES; FISSION YEAST; CRYSTAL-STRUCTURE; IN-VIVO

Štítky

kontrola MP, MP, rivok

Příznaky

Mezinárodní význam, Recenzováno

Změněno: 5. 12. 2014 08:02, Martina Prášilová

Anotace

V originále

Phosphorylation of the RNA polymerase II C-terminal domain (CTD) by cyclin-dependent kinases is important for productive transcription. Here we determine the crystal structure of Cdk12/CycK and analyse its requirements for substrate recognition. Active Cdk12/CycK is arranged in an open conformation similar to that of Cdk9/CycT but different from those of cell cycle kinases. Cdk12 contains a C-terminal extension that folds onto the N- and C-terminal lobes thereby contacting the ATP ribose. The interaction is mediated by an HE motif followed by a polybasic cluster that is conserved in transcriptional CDKs. Cdk12/CycK showed the highest activity on a CTD substrate prephosphorylated at position Ser7, whereas the common Lys7 substitution was not recognized. Flavopiridol is most potent towards Cdk12 but was still 10-fold more potent towards Cdk9. T-loop phosphorylation of Cdk12 required coexpression with a Cdk-activating kinase. These results suggest the regulation of Pol II elongation by a relay of transcriptionally active CTD kinases.

Návaznosti

ED1.1.00/02.0068, projekt VaV

Název: CEITEC - central european institute of technology

GA14-09979S, projekt VaV

Název: Role Cdk12 a C-terminální domény RNA polymerázy II v transkripcně regulovaném procesu genomové nestability

Investor: Grantová agentura ČR, Role Cdk12 a C-terminální domény RNA polymerázy II v transkripcně regulovaném procesu genomové nestability

Citovat

BÖSKEN, Christian A.; Lucas FARNUNG; Corinna HINTERMAIR; Miriam Merzel SCHACHTER; Karin VOGEL- BACHMAYR; Dalibor BLAŽEK; Kanchan ANAND; Robert P. FISHER; Dirk EICK a Matthias GEYER. The structure and substrate specificity of human Cdk12/Cyclin K. NATURE COMMUNICATIONS. London: Nature Publishing Group, 2014, roč. 5, č. 3505, s. "nestránkováno", 14 s. ISSN 2041-1723. Dostupné z: https://doi.org/10.1038/ncomms4505.

@article{1186174,
   author = {Bösken, Christian A. and Farnung, Lucas and Hintermair, Corinna and Schachter, Miriam Merzel and Vogeland Bachmayr, Karin and Blažek, Dalibor and Anand, Kanchan and Fisher, Robert P. and Eick, Dirk and Geyer, Matthias},
   article_location = {London},
   article_number = {3505},
   doi = {https://doi.org/10.1038/ncomms4505},
   keywords = {RNA-POLYMERASE-II; C-TERMINAL DOMAIN; CAPPING ENZYME RECRUITMENT; CYCLIN-DEPENDENT KINASE-9; CTD CODE; P-TEFB; PROTEIN-KINASES; FISSION YEAST; CRYSTAL-STRUCTURE; IN-VIVO},
   language = {eng},
   issn = {2041-1723},
   journal = {NATURE COMMUNICATIONS},
   title = {The structure and substrate specificity of human Cdk12/Cyclin K},
   url = {http://www.nature.com/ncomms/2014/140324/ncomms4505/pdf/ncomms4505.pdf},
   volume = {5},
   year = {2014}
}

TY  - JOUR
ID  - 1186174
AU  - Bösken, Christian A. - Farnung, Lucas - Hintermair, Corinna - Schachter, Miriam Merzel - Vogel- Bachmayr, Karin - Blažek, Dalibor - Anand, Kanchan - Fisher, Robert P. - Eick, Dirk - Geyer, Matthias
PY  - 2014
TI  - The structure and substrate specificity of human Cdk12/Cyclin K
JF  - NATURE COMMUNICATIONS
VL  - 5
IS  - 3505
SP  - "nestránkováno"
EP  - "nestránkováno"
PB  - Nature Publishing Group
SN  - 20411723
KW  - RNA-POLYMERASE-II
KW  - C-TERMINAL DOMAIN
KW  - CAPPING ENZYME RECRUITMENT
KW  - CYCLIN-DEPENDENT KINASE-9
KW  - CTD CODE
KW  - P-TEFB
KW  - PROTEIN-KINASES
KW  - FISSION YEAST
KW  - CRYSTAL-STRUCTURE
KW  - IN-VIVO
UR  - http://www.nature.com/ncomms/2014/140324/ncomms4505/pdf/ncomms4505.pdf
L2  - http://www.nature.com/ncomms/2014/140324/ncomms4505/pdf/ncomms4505.pdf
N2  - Phosphorylation of the RNA polymerase II C-terminal domain (CTD) by cyclin-dependent kinases is important for productive transcription. Here we determine the crystal structure of Cdk12/CycK and analyse its requirements for substrate recognition. Active Cdk12/CycK is arranged in an open conformation similar to that of Cdk9/CycT but different from those of cell cycle kinases. Cdk12 contains a C-terminal extension that folds onto the N- and C-terminal lobes thereby contacting the ATP ribose. The interaction is mediated by an HE motif followed by a polybasic cluster that is conserved in transcriptional CDKs. Cdk12/CycK showed the highest activity on a CTD substrate prephosphorylated at position Ser7, whereas the common Lys7 substitution was not recognized. Flavopiridol is most potent towards Cdk12 but was still 10-fold more potent towards Cdk9. T-loop phosphorylation of Cdk12 required coexpression with a Cdk-activating kinase. These results suggest the regulation of Pol II elongation by a relay of transcriptionally active CTD kinases.
ER  -

BÖSKEN, Christian A.; Lucas FARNUNG; Corinna HINTERMAIR; Miriam Merzel SCHACHTER; Karin VOGEL- BACHMAYR; Dalibor BLAŽEK; Kanchan ANAND; Robert P. FISHER; Dirk EICK a Matthias GEYER. The structure and substrate specificity of human Cdk12/Cyclin K. \textit{NATURE COMMUNICATIONS}. London: Nature Publishing Group, 2014, roč.~5, č.~3505, s.~''nestránkováno'', 14 s. ISSN~2041-1723. Dostupné z: https://doi.org/10.1038/ncomms4505.

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