Structural and Functional Analysis of the Cdk13/Cyclin K
Complex

J 2016

Structural and Functional Analysis of the Cdk13/Cyclin K Complex

GREIFENBERG, Ann Katrin; Dana HÖNIG; Květa PILAŘOVÁ; Robert DÜSTER; Koen BARTHOLOMEEUSEN et. al.

Základní údaje

Originální název

Structural and Functional Analysis of the Cdk13/Cyclin K Complex

Autoři

GREIFENBERG, Ann Katrin; Dana HÖNIG; Květa PILAŘOVÁ; Robert DÜSTER; Koen BARTHOLOMEEUSEN; Christian A. BOSKEN; Kanchan ANAND; Dalibor BLAŽEK a Matthias GEYER

Vydání

Cell Reports, CAMBRIDGE, Cell Press, 2016, 2211-1247

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

Genetika a molekulární biologie

Stát vydavatele

Spojené státy

Utajení

není předmětem státního či obchodního tajemství

Odkazy

URL

Impakt faktor

Impact factor: 8.282

Kód RIV

RIV/00216224:14740/16:00088066

Organizační jednotka

Středoevropský technologický institut

DOI

https://doi.org/10.1016/j.celrep.2015.12.025

UT WoS

000368101600015

EID Scopus

2-s2.0-84955368501

Klíčová slova anglicky

RNA-POLYMERASE-II; P-TEFB; TRANSCRIPTION CYCLE; OVARIAN-CARCINOMA; MESSENGER-RNA; PHOSPHORYLATION; KINASE; CTD; ELONGATION; CDK12

Štítky

rivok

Změněno: 5. 8. 2016 10:26, Mgr. Eva Špillingová

Anotace

V originále

Cyclin-dependent kinases regulate the cell cycle and transcription in higher eukaryotes. We have determined the crystal structure of the transcription kinase Cdk13 and its Cyclin K subunit at 2.0 angstrom resolution. Cdk13 contains a C-terminal extension helix composed of a polybasic cluster and a DCHEL motif that interacts with the bound ATP. Cdk13/CycK phosphorylates both Ser5 and Ser2 of the RNA polymerase II C-terminal domain (CTD) with a preference for Ser7 pre-phosphorylations at a C-terminal position. The peptidyl-prolyl isomerase Pin1 does not change the phosphorylation specificities of Cdk9, Cdk12, and Cdk13 but interacts with the phosphorylated CTD through its WW domain. Using recombinant proteins, we find that flavopiridol inhibits Cdk7 more potently than it does Cdk13. Gene expression changes after knockdown of Cdk13 or Cdk12 are markedly different, with enrichment of growth signaling pathways for Cdk13-dependent genes. Together, our results provide insights into the structure, function, and activity of human Cdk13/CycK.

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

GREIFENBERG, Ann Katrin; Dana HÖNIG; Květa PILAŘOVÁ; Robert DÜSTER; Koen BARTHOLOMEEUSEN; Christian A. BOSKEN; Kanchan ANAND; Dalibor BLAŽEK a Matthias GEYER. Structural and Functional Analysis of the Cdk13/Cyclin K Complex. Cell Reports. CAMBRIDGE: Cell Press, 2016, roč. 14, č. 2, s. 320-331. ISSN 2211-1247. Dostupné z: https://doi.org/10.1016/j.celrep.2015.12.025.

@article{1350913,
   author = {Greifenberg, Ann Katrin and Hönig, Dana and Pilařová, Květa and Düster, Robert and Bartholomeeusen, Koen and Bosken, Christian A. and Anand, Kanchan and Blažek, Dalibor and Geyer, Matthias},
   article_location = {CAMBRIDGE},
   article_number = {2},
   doi = {https://doi.org/10.1016/j.celrep.2015.12.025},
   keywords = {RNA-POLYMERASE-II; P-TEFB; TRANSCRIPTION CYCLE; OVARIAN-CARCINOMA; MESSENGER-RNA; PHOSPHORYLATION; KINASE; CTD; ELONGATION; CDK12},
   language = {eng},
   issn = {2211-1247},
   journal = {Cell Reports},
   title = {Structural and Functional Analysis of the Cdk13/Cyclin K Complex},
   url = {http://www.sciencedirect.com/science/article/pii/S2211124715014382},
   volume = {14},
   year = {2016}
}

TY  - JOUR
ID  - 1350913
AU  - Greifenberg, Ann Katrin - Hönig, Dana - Pilařová, Květa - Düster, Robert - Bartholomeeusen, Koen - Bosken, Christian A. - Anand, Kanchan - Blažek, Dalibor - Geyer, Matthias
PY  - 2016
TI  - Structural and Functional Analysis of the Cdk13/Cyclin K Complex
JF  - Cell Reports
VL  - 14
IS  - 2
SP  - 320-331
EP  - 320-331
PB  - Cell Press
SN  - 22111247
KW  - RNA-POLYMERASE-II
KW  - P-TEFB
KW  - TRANSCRIPTION CYCLE
KW  - OVARIAN-CARCINOMA
KW  - MESSENGER-RNA
KW  - PHOSPHORYLATION
KW  - KINASE
KW  - CTD
KW  - ELONGATION
KW  - CDK12
UR  - http://www.sciencedirect.com/science/article/pii/S2211124715014382
L2  - http://www.sciencedirect.com/science/article/pii/S2211124715014382
N2  - Cyclin-dependent kinases regulate the cell cycle and transcription in higher eukaryotes. We have determined the crystal structure of the transcription kinase Cdk13 and its Cyclin K subunit at 2.0 angstrom resolution. Cdk13 contains a C-terminal extension helix composed of a polybasic cluster and a DCHEL motif that interacts with the bound ATP. Cdk13/CycK phosphorylates both Ser5 and Ser2 of the RNA polymerase II C-terminal domain (CTD) with a preference for Ser7 pre-phosphorylations at a C-terminal position. The peptidyl-prolyl isomerase Pin1 does not change the phosphorylation specificities of Cdk9, Cdk12, and Cdk13 but interacts with the phosphorylated CTD through its WW domain. Using recombinant proteins, we find that flavopiridol inhibits Cdk7 more potently than it does Cdk13. Gene expression changes after knockdown of Cdk13 or Cdk12 are markedly different, with enrichment of growth signaling pathways for Cdk13-dependent genes. Together, our results provide insights into the structure, function, and activity of human Cdk13/CycK.
ER  -

GREIFENBERG, Ann Katrin; Dana HÖNIG; Květa PILAŘOVÁ; Robert DÜSTER; Koen BARTHOLOMEEUSEN; Christian A. BOSKEN; Kanchan ANAND; Dalibor BLAŽEK a Matthias GEYER. Structural and Functional Analysis of the Cdk13/Cyclin K Complex. \textit{Cell Reports}. CAMBRIDGE: Cell Press, 2016, roč.~14, č.~2, s.~320-331. ISSN~2211-1247. Dostupné z: https://doi.org/10.1016/j.celrep.2015.12.025.

Přehled o publikaci