Effects of phosphorylation by protein kinase CK2 on the human basal components of the RNA polymerase II transcription machinery

2004 ◽  
Vol 93 (1) ◽  
pp. 2-10 ◽  
Author(s):  
Mar�a Eugenia Cabrejos ◽  
Catherine C. Allende ◽  
Edio Maldonado
2020 ◽  
Vol 21 (9) ◽  
pp. 3354 ◽  
Author(s):  
Ryan D. Martin ◽  
Terence E. Hébert ◽  
Jason C. Tanny

Inhibitors targeting the general RNA polymerase II (RNAPII) transcription machinery are candidate therapeutics in cancer and other complex diseases. Here, we review the molecular targets and mechanisms of action of these compounds, framing them within the steps of RNAPII transcription. We discuss the effects of transcription inhibitors in vitro and in cellular models (with an emphasis on cancer), as well as their efficacy in preclinical and clinical studies. We also discuss the rationale for inhibiting broadly acting transcriptional regulators or RNAPII itself in complex diseases.


2001 ◽  
Vol 276 (50) ◽  
pp. 47150-47153 ◽  
Author(s):  
Tilman Borggrefe ◽  
Ralph Davis ◽  
Avital Bareket-Samish ◽  
Roger D. Kornberg

TAP tags and dot blot analysis have been used to measure the amounts of RNA polymerase II transcription proteins in crude yeast extracts. The measurements showed comparable amounts of RNA polymerase II, TFIIE, and TFIIF, lower levels of TBP and TFIIB, and still lower levels of Mediator and TFIIH. These findings are consistent with the presumed roles of the transcription proteins, but do not support the idea of their recruitment in a single large complex to RNA polymerase II promoters. The approach employed here can be readily extended to quantitative analysis of the entire yeast proteome.


2004 ◽  
Vol 24 (11) ◽  
pp. 4734-4742 ◽  
Author(s):  
Chika Sawa ◽  
Eduard Nedea ◽  
Nevan Krogan ◽  
Tadashi Wada ◽  
Hiroshi Handa ◽  
...  

ABSTRACT Bromodomain factor 1 (Bdf1) associates with Saccharomyces cerevisiae TFIID and corresponds to the C-terminal half of higher eukaryotic TAF1. It also associates with the SWR-C complex, which is important for Htz1 deposition. Bdf1 binds preferentially to acetylated histone H4. Bdf1 is phosphorylated, but the mechanism and significance of this modification have been unclear. Two distinct regions within Bdf1 are phosphorylated; one is just C terminal to the bromodomains and the other is near the C terminus. Mutational analysis shows that phosphorylation is necessary for Bdf1 function in vivo. Endogenous protein kinase CK2 purifies with Bdf1 and phosphorylates both domains. A similar mechanism may be responsible for phosphorylation of the C-terminal region of mammalian TAF1. These findings suggest that CK2 phosphorylation of Bdf1 may regulate RNA polymerase II transcription and/or chromatin structure.


2001 ◽  
Vol 382 (8) ◽  
pp. 1103-1107 ◽  
Author(s):  
Roger D. Kornberg

Abstract Seven purified proteins may be combined to reconstitute regulated, promoterdependent RNA polymerase II transcription: five general transcription factors, Mediator, and RNA polymerase II. The entire system has been conserved across species from yeast to humans. The structure of RNA polymerase II, consisting of 10 polypeptides with a mass of about 500 kDa, has been determined at atomic resolution. On the basis of this structure, that of an actively transcribing RNA polymerase II complex has been determined as well.


2020 ◽  
Vol 34 (7-8) ◽  
pp. 465-488 ◽  
Author(s):  
Allison C. Schier ◽  
Dylan J. Taatjes

Oncotarget ◽  
2020 ◽  
Vol 11 (7) ◽  
pp. 699-726 ◽  
Author(s):  
Sonia Zicari ◽  
Adhikarimayum Lakhikumar Sharma ◽  
Geetaram Sahu ◽  
Larisa Dubrovsky ◽  
Lin Sun ◽  
...  

2007 ◽  
Vol 282 (38) ◽  
pp. 27887-27896 ◽  
Author(s):  
Liping Gu ◽  
Rhonda Husain-Ponnampalam ◽  
Susanne Hoffmann-Benning ◽  
R. William Henry

Human U6 small nuclear RNA gene transcription by RNA polymerase III requires the general transcription factor SNAPC, which binds to human small nuclear RNA core promoter elements and nucleates pre-initiation complex assembly with the Brf2-TFIIIB complex. Multiple components in this pathway are phosphorylated by the protein kinase CK2, including the Bdp1 subunit of the Brf2-TFIIIB complex, and RNA polymerase III, with negative and positive outcomes for U6 transcription, respectively. However, a role for CK2 phosphorylation of SNAPC in U6 transcription has not been defined. In this report, we investigated the role of CK2 in modulating the transcriptional properties of SNAPC and demonstrate that within SNAPC, CK2 phosphorylates the N-terminal half of the SNAP190 subunit at two regions (amino acids 20-63 and 514-545) that each contain multiple CK2 consensus sites. SNAP190 phosphorylation by CK2 inhibits both SNAPC DNA binding and U6 transcription activity. Mutational analyses of SNAP190 support a model wherein CK2 phosphorylation triggers an allosteric inhibition of the SNAP190 Myb DNA binding domain.


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