scholarly journals Phosphorylation of OGFOD1 by Cell Cycle-Dependent Kinase 7/9 Enhances the Transcriptional Activity of RNA Polymerase II in Breast Cancer Cells

Cancers ◽  
2021 ◽  
Vol 13 (14) ◽  
pp. 3418
Author(s):  
Han-Teo Lee ◽  
Il-Hwan Lee ◽  
Jae-Hwan Kim ◽  
Sangho Lee ◽  
Sojung Kwak ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Cycle ◽  
Tumor Growth ◽  
Rna Polymerase ◽  
Cancer Cells ◽  
Rna Polymerase Ii ◽  
Transcriptional Activation ◽  
Breast Cancer Cells ◽  
Transcriptional Activity ◽  
Cycle Dependent

2-oxoglutarate and iron-dependent oxygenase domain-containing protein 1 (OGFOD1) expression is upregulated in a variety of cancers and has been related to poor prognosis. However, despite this significance to cancer progression, the precise oncogenic mechanism of OGFOD1 is not understood. We demonstrated that OGFOD1 plays a role in enhancing the transcriptional activity of RNA polymerase II in breast cancer cells. OGFOD1 directly binds to the C-terminal domain of RNA polymerase II to alter phosphorylation status. The elimination of OGFOD1 resulted in decreased tumor development. Additionally, cell cycle-dependent kinase 7 and cell cycle-dependent kinase 9, critical enzymes for activating RNA polymerase II, phosphorylated serine 256 of OGFOD1, whereas a non-phosphorylated mutant OGFOD1 failed to enhance transcriptional activation and tumor growth. Consequently, OGFOD1 helps promote tumor growth by enhancing RNA polymerase II, whereas simultaneous phosphorylation of OGFOD1 by CDK enzymes is essential in stimulating RNA polymerase II-mediated transcription both in vitro and in vivo, and expression of target genes.

Cell-cycle-dependent expression of the large Ca2+-activated K+ channels in breast cancer cells

2004 ◽  
Vol 316 (1) ◽  
pp. 244-251 ◽  
Author(s):  
Halima Ouadid-Ahidouch ◽  
Morad Roudbaraki ◽  
Ahmed Ahidouch ◽  
Philippe Delcourt ◽  
Natalia Prevarskaya
Keyword(s):  
Breast Cancer ◽  
Cell Cycle ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
K Channels ◽  
Cycle Dependent

scholarly journals FHL2 Regulates Cell Cycle-Dependent and Doxorubicin-Induced p21Cip1/Waf1 Expression in Breast Cancer Cells

Cell Cycle ◽  
2007 ◽  
Vol 6 (14) ◽  
pp. 1779-1788 ◽  
Author(s):  
Bernd T. Martin ◽  
Kai Kleiber ◽  
Viktor Wixler ◽  
Monika Raab ◽  
Brigitte Zimmer ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Cycle ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Cycle Dependent

scholarly journals Arginine citrullination at the C-terminal domain controls RNA polymerase II transcription

2017 ◽  
Author(s):  
Priyanka Sharma ◽  
Antonios Lioutas ◽  
Narcis Fernandez-Fuentes ◽  
Javier Quilez ◽  
José Carbonell-Caballero ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Rna Polymerase ◽  
Cancer Cells ◽  
Rna Polymerase Ii ◽  
Breast Cancer Cells ◽  
Arginine Deiminase ◽  
Peptidyl Arginine Deiminase ◽  
Terminal Domain ◽  
Carboxy Terminal Domain ◽  
Carboxy Terminal

HighlightsPeptidyl arginine deiminase 2 (PADI2) citrullinates arginine1810 (cit1810) present at carboxy-terminal domain of RNA polymerase II (RNAP2-CTD).PADI2 and R1810 of RNAP2-CTD regulate transcription and proliferation of breast cancer cells.Absence of cit1810 at RNAP2-CTD leads to RNAP2 accumulation at proximal promoter regions.Cit1810 at RNAP2-CTD facilitate interaction with P-TFEb complex.SUMMARYThe post-translational modification of key residues at the carboxy-terminal domain of RNA polymerase II (RNAP2-CTD), coordinates transcription, splicing, and RNA processing by modulating its capacity to act as a landing platform for a variety of protein complexes. Here, we identify a new modification at the CTD, the deimination of arginine and its conversion to citrulline by peptidyl arginine deiminase 2 (PADI2), an enzyme that has been associated with several diseases including cancer. We show that among PADI family members, only PADI2 citrullinates R1810 (Cit1810) at repeat 31 of the CTD. Depletion of PADI2 or loss of R1810 result in accumulation of RNAP2 at transcription start sites, reduced gene expression and inhibition of cell proliferation. Cit1810 is needed for interaction with the P-TEFb (positive transcription elongation factor b) kinase complex and for its recruitment to chromatin. In this way, CTD-Cit1810 favors RNAP2 pause release and efficient transcription in breast cancer cells.

scholarly journals Cell cycle-dependent regulation of the bi-directional overlapping promoter of human BRCA2/ZAR2 genes in breast cancer cells

2010 ◽  
Vol 9 (1) ◽  
pp. 50 ◽  
Author(s):  
Smita Misra ◽  
Shvetank Sharma ◽  
Anupriya Agarwal ◽  
Sheetal V Khedkar ◽  
Manish K Tripathi ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Cycle ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Cycle Dependent

scholarly journals BRG1 Activates Proliferation and Transcription of Cell Cycle-Dependent Genes in Breast Cancer Cells

Cancers ◽  
2020 ◽  
Vol 12 (2) ◽  
pp. 349 ◽  
Author(s):  
Maciej Sobczak ◽  
Julita Pietrzak ◽  
Tomasz Płoszaj ◽  
Agnieszka Robaszkiewicz
Keyword(s):  
Breast Cancer ◽  
Cell Cycle ◽  
Cancer Cells ◽  
Cell Lines ◽  
Gene Transcription ◽  
Breast Cancer Cells ◽  
Cell Cycle Progression ◽  
Gene Promoters ◽  
Cycle Progression ◽  
Cycle Dependent

Cancer malignancy is usually characterized by unlimited self-renewal. In some types of advanced tumors that are rapidly dividing, gene expression profiles depict elevations in pro-proliferative genes accompanied by coordinately elevated transcription of factors responsible for removal of DNA lesions. In our studies, fast proliferating breast cancer cell lines (MDA-MB-231 and MCF7), BRG1, a component of the SWI/SNF complex, emerges as an activator of functionally-linked genes responsible for activities such as mitotic cell divisions and DNA repair. Products of at least some of them are considerably overrepresented in breast cancer cells and BRG1 facilitates growth of MCF7 and MDA-MB-231 cell lines. BRG1 occurs at the promoters of genes such as CDK4, LIG1, and NEIL3, which are transcriptionally controlled by cell cycle progression and highly acetylated by EP300 in proliferating cells. As previously documented, in dividing cells BRG1 directly activates gene transcription by evicting EP300 modified nucleosomes from the promoters and, thereby, relaxing chromatin. However, the deficiency of BRG1 or EP300 activity for 48 h leads to cell growth arrest and to chromatin compaction, but also to the assembly of RB1/HDAC1/EZH2 complexes at the studied cell cycle-dependent gene promoters. Epigenetic changes include histone deacetylation and accumulation of H3K27me trimethylation, both known to repress transcription. Cell cycle arrest in G1 by inhibition of CDK4/6 phenocopies the effect of the long-term BRG1 inhibition on the chromatin structure. These results suggest that BRG1 may control gene transcription also by promoting expression of genes responsible for cell cycle progression in the studied breast cancer cells. In the current study, we show that BRG1 binding occurs at the promoters of functionally linked genes in proliferating breast cancer cells, revealing a new mechanism by which BRG1 defines gene transcription.

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