Regulatory functions of the Mediator kinases CDK8 and CDK19

被引：94

作者：

Fant, Charli B. ^{[1
]}

Taatjes, Dylan J. ^{[1
]}

机构：

[1] Univ Colorado, Dept Biochem, Boulder, CO 80309 USA

来源：

TRANSCRIPTION-AUSTIN | 2019年 / 10卷 / 02期

基金：

美国国家科学基金会;

关键词：

Mediator kinase; enhancer; transcription; RNA polymerase II; chromatin; RNA-POLYMERASE-II; PLURIPOTENT STEM-CELLS; MASTER TRANSCRIPTION FACTORS; DEPENDENT PROTEIN-KINASE; SMALL-MOLECULE; PSEUDOHYPHAL DIFFERENTIATION; MODULE ASSOCIATION; SUPER-ENHANCERS; GENE-EXPRESSION; CANCER;

D O I：

10.1080/21541264.2018.1556915

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

The Mediator-associated kinases CDK8 and CDK19 function in the context of three additional proteins: CCNC and MED12, which activate CDK8/CDK19 kinase function, and MED13, which enables their association with the Mediator complex. The Mediator kinases affect RNA polymerase II (pol II) transcription indirectly, through phosphorylation of transcription factors and by controlling Mediator structure and function. In this review, we discuss cellular roles of the Mediator kinases and mechanisms that enable their biological functions. We focus on sequence-specific, DNA-binding transcription factors and other Mediator kinase substrates, and how CDK8 or CDK19 may enable metabolic and transcriptional reprogramming through enhancers and chromatin looping. We also summarize Mediator kinase inhibitors and their therapeutic potential. Throughout, we note conserved and divergent functions between yeast and mammalian CDK8, and highlight many aspects of kinase module function that remain enigmatic, ranging from potential roles in pol II promoter-proximal pausing to liquid-liquid phase separation.

引用

页码：76 / 90

页数：15

共 160 条

[1] CDK8 Maintains Tumor Dedifferentiation and Embryonic Stem Cell Pluripotency [J].

Adler, Adam S. ;

McCleland, Mark L. ;

Truong, Tom ;

Lau, Shari ;

Modrusan, Zora ;

Soukup, Tim M. ;

Roose-Girma, Merone ;

Blackwood, Elizabeth M. ;

Firestein, Ron .

CANCER RESEARCH, 2012, 72 (08) :2129-2139

[2] Metabolism in physiological cell proliferation and differentiation [J].

Agathocleous, Michalis ;

Harris, William A. .

TRENDS IN CELL BIOLOGY, 2013, 23 (10) :484-492

[3] Enhancer hubs and loop collisions identified from single-allele topologies [J].

Allahyar, Amin ;

Vermeulen, Carlo ;

Bouwman, Britta A. M. ;

Krijger, Peter H. L. ;

Verstegen, Marjon J. A. M. ;

Geeven, Geert ;

van Kranenburg, Melissa ;

Pieterse, Mark ;

Straver, Roy ;

Haarhuis, Judith H. I. ;

Jalink, Kees ;

Teunissen, Hans ;

Renkens, Ivo J. ;

Kloosterman, Wigard P. ;

Rowland, Benjamin D. ;

de Wit, Elzo ;

de Ridder, Jeroen ;

de Laat, Wouter .

NATURE GENETICS, 2018, 50 (08) :1151-+

[4] The Mediator complex: a central integrator of transcription [J].

Allen, Benjamin L. ;

Taatjes, Dylan J. .

NATURE REVIEWS MOLECULAR CELL BIOLOGY, 2015, 16 (03) :155-166

[5] A MED13-dependent skeletal muscle gene program controls systemic glucose homeostasis and hepatic metabolism [J].

Amoasii, Leonela ;

Holland, William ;

Sanchez-Ortiz, Efrain ;

Baskin, Kedryn K. ;

Pearson, Mackenzie ;

Burgess, Shawn C. ;

Nelson, Benjamin R. ;

Bassel-Duby, Rhonda ;

Olson, Eric N. .

GENES & DEVELOPMENT, 2016, 30 (04) :434-446

[6] An atlas of active enhancers across human cell types and tissues [J].

Andersson, Robin ;

Gebhard, Claudia ;

Miguel-Escalada, Irene ;

Hoof, Ilka ;

Bornholdt, Jette ;

Boyd, Mette ;

Chen, Yun ;

Zhao, Xiaobei ;

Schmidl, Christian ;

Suzuki, Takahiro ;

Ntini, Evgenia ;

Arner, Erik ;

Valen, Eivind ;

Li, Kang ;

Schwarzfischer, Lucia ;

Glatz, Dagmar ;

Raithel, Johanna ;

Lilje, Berit ;

Rapin, Nicolas ;

Bagger, Frederik Otzen ;

Jorgensen, Mette ;

Andersen, Peter Refsing ;

Bertin, Nicolas ;

Rackham, Owen ;

Burroughs, A. Maxwell ;

Baillie, J. Kenneth ;

Ishizu, Yuri ;

Shimizu, Yuri ;

Furuhata, Erina ;

Maeda, Shiori ;

Negishi, Yutaka ;

Mungall, Christopher J. ;

Meehan, Terrence F. ;

Lassmann, Timo ;

Itoh, Masayoshi ;

Kawaji, Hideya ;

Kondo, Naoto ;

Kawai, Jun ;

Lennartsson, Andreas ;

Daub, Carsten O. ;

Heutink, Peter ;

Hume, David A. ;

Jensen, Torben Heick ;

Suzuki, Harukazu ;

Hayashizaki, Yoshihide ;

Mueller, Ferenc ;

Forrest, Alistair R. R. ;

Carninci, Piero ;

Rehli, Michael ;

Sandelin, Albin .

NATURE, 2014, 507 (7493) :455-+

[7] Genome-wide location of the coactivator mediator: Binding without activation and transient Cdk8 interaction on DNA [J].

Andrau, JC ;

van de Pasch, L ;

Lijnzaad, P ;

Bijma, T ;

Koerkamp, MG ;

van de Peppel, J ;

Werner, M ;

Holstege, FCP .

MOLECULAR CELL, 2006, 22 (02) :179-192

[8] MED12 Regulates HSC-Specific Enhancers Independently of Mediator Kinase Activity to Control Hematopoiesis [J].

Aranda-Orgilles, Beatriz ;

Saldana-Meyer, Ricardo ;

Wang, Eric ;

Trompouki, Eirini ;

Fassl, Anne ;

Lau, Stephanie ;

Mullenders, Jasper ;

Rocha, Pedro P. ;

Raviram, Ramya ;

Guillamot, Maria ;

Sanchez-Diaz, Maria ;

Wang, Kun ;

Kayembe, Clarisse ;

Zhang, Nan ;

Amoasii, Leonela ;

Choudhuri, Avik ;

Skok, Jane A. ;

Schober, Markus ;

Reinberg, Danny ;

Sicinski, Piotr ;

Schrewe, Heinrich ;

Tsirigos, Aristotelis ;

Zon, Leonard I. ;

Aifantis, Iannis .

CELL STEM CELL, 2016, 19 (06) :784-799

[9] Transcribed enhancers lead waves of coordinated transcription in transitioning mammalian cells [J].

Arner, Erik ;

Daub, Carsten O. ;

Vitting-Seerup, Kristoffer ;

Andersson, Robin ;

Lilje, Berit ;

Drablos, Finn ;

Lennartsson, Andreas ;

Roennerblad, Michelle ;

Hrydziuszko, Olga ;

Vitezic, Morana ;

Freeman, Tom C. ;

Alhendi, Ahmad M. N. ;

Arner, Peter ;

Axton, Richard ;

Baillie, J. Kenneth ;

Beckhouse, Anthony ;

Bodega, Beatrice ;

Briggs, James ;

Brombacher, Frank ;

Davis, Margaret ;

Detmar, Michael ;

Ehrlund, Anna ;

Endoh, Mitsuhiro ;

Eslami, Afsaneh ;

Fagiolini, Michela ;

Fairbairn, Lynsey ;

Faulkner, Geoffrey J. ;

Ferrai, Carmelo ;

Fisher, Malcolm E. ;

Forrester, Lesley ;

Goldowitz, Daniel ;

Guler, Reto ;

Ha, Thomas ;

Hara, Mitsuko ;

Herlyn, Meenhard ;

Ikawa, Tomokatsu ;

Kai, Chieko ;

Kawamoto, Hiroshi ;

Khachigian, Levon M. ;

Klinken, S. Peter ;

Kojima, Soichi ;

Koseki, Haruhiko ;

Klein, Sarah ;

Mejhert, Niklas ;

Miyaguchi, Ken ;

Mizuno, Yosuke ;

Morimoto, Mitsuru ;

Morris, Kelly J. ;

Mummery, Christine ;

Nakachi, Yutaka .

SCIENCE, 2015, 347 (6225) :1010-1014

[10] A Kinase-Independent Role for Cyclin-Dependent Kinase 19 in p53 Response [J].

Audetat, K. Audrey ;

Galbraith, Matthew D. ;

Odell, Aaron T. ;

Lee, Thomas ;

Pandey, Ahwan ;

Espinosa, Joaquin M. ;

Dowell, Robin D. ;

Taatjes, Dylan J. .

MOLECULAR AND CELLULAR BIOLOGY, 2017, 37 (13)

← 1 2 3 4 5 6 7 8 9 10 →