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Introduction to Genomics
Published in Altuna Akalin, Computational Genomics with R, 2020
In order to answer this question, we have to dig a little deeper into the transcription concept we introduced via the central dogma. The first step in a process of information transfer - the production of an RNA copy of a part of the DNA sequence - is called transcription. This task is carried out by the RNA polymerase enzyme. RNA polymerase-dependent initiation of transcription is enabled by the existence of a specific region in the sequence of DNA - a core promoter. Core promoters are regions of DNA that promote transcription and are found upstream from the start site of transcription. In eukaryotes, several proteins, called general transcription factors, recognize and bind to core promoters and form a pre-initiation complex. RNA polymerases recognize these complexes and initiate synthesis of RNAs, the polymerase travels along the template DNA and makes an RNA copy (Hager et al., 2009). After mRNA is produced it is often spliced by spliceosome. The sections, called ‘introns’, are removed and sections called ‘exons’ left in. Then, the remaining mRNA is translated into proteins. Which exons will be part of the final mature transcript can also be regulated and creates diversity in protein structure and function (See Figure 1.3).
REGULATORY MECHANISMS
Published in David M. Gibson, Robert A. Harris, Metabolic Regulation in Mammals, 2001
David M. Gibson, Robert A. Harris
Some studies suggest that many of the general transcription factors exist as a pre-assembled complex which is guided into its final orientation on the promoter by the binding of the unique transcription factors/activators to their cognate DNA elements in the enhancer region. Complementary binding and linked conformational changes among all protein components position the RNA polymerase enzyme at the initiation site. Bridging the gap between the upstream specific transcription factors and
The Cell and Cell Division
Published in Anthony R. Mundy, John M. Fitzpatrick, David E. Neal, Nicholas J. R. George, The Scientific Basis of Urology, 2010
In addition to these specific transcription factors, general transcription factors are also required. Several proto-oncogenes are transcription factors. Fos and jun combine when phosphorylated to form the AP-1 protein, which functions as a transcription factor. Several growth factors interact through ras to activate MAP kinase (mitogen-activated kinase). MAP kinase phosphorylates a protein called Elk-1, which itself activates the transcription of fos.
The roles of TPL in hematological malignancies
Published in Hematology, 2023
Tingyun Xu, Yiwei Zhu, Shuaishuai Ge, Song-Bai Liu
CD26 is a type II glycoprotein that has been used as a poor prognostic factor, and CD26-positive cells have been found to be highly expressed in various hematologic tumors [107–109]. Humanized anti-CD26 monoclonal antibody (YS110) has been coupled to TR1, a modified version of TPL at the sulfhydryl (SH) group, to produce an antibody–drug conjugate Y-TR1. Y-TR1 binds to CD26 on the cell surface and can cause cell death through immune-mediated cytotoxicity [110, 111]. Y-TR1 significantly inhibits the proliferation of CD26-positive tumor cells without affecting CD26-negative cells. YS110 can be internalized to the nucleus to inhibit cell proliferation by suppressing the transcription of POLR2A, a subunit of RNA polymerase II. Y-TR1 inhibits cell proliferation by inhibiting general transcription factor IIH (TFIIH), which is required for the transcription of RNA polymerase II (Pol II) [111, 112].
Sp1 Controls the Basal Level of Interleukin-34 Transcription
Published in Immunological Investigations, 2023
Minggui Lin, Xingyun Liu, Xinhui Zhang, Huimin Wang, Yu Fang, Xiaoting Wu, Anqi Yin, Wanqing Yang, Dong Zhang, Miaomiao Li, Ling Zhang, Songcheng Ying
Human IL-34 mRNA is expressed in a variety of tissues, including heart, brain, lung, liver, kidney, spleen, thymus, testes, ovary, small intestine, prostate, and colon (Lin et al. 2008). Growing evidence show that IL-34 expression may be upregulated or downregulated by some stimuli (Baghdadi et al. 2017; Baghdadi, Umeyama et al. 2018; Ge et al. 2019; Otsuka et al. 2021). However, the regulation of IL-34 basal expression is largely unknown. In this study, we found that the basal level of IL-34 transcription was controlled by general transcription factor Sp1. It is of note that IL-34 protein is expressed selectively in particular cell types, such as keratinocytes in the epidermis and neurons in the brain (Greter et al. 2012; Wang et al. 2012). Sp1 can interact with other transcription factors to mediate tissue or lineage-specific transcriptional regulation (O’Connor et al. 2016; Resendes and Rosmarin 2004). It is necessary to identify whether Sp1 interacts with other transcription factors in the skin and brain and which tissue or cell-specific transcription factor may contribute to the differential expression of IL-34 in different cells.
A patent review of cyclin-dependent kinase 7 (CDK7) inhibitors (2018-2022)
Published in Expert Opinion on Therapeutic Patents, 2023
Markéta Kovalová, Joseph Peter Baraka, Václav Mik, Radek Jorda, Lei Luo, Hao Shao, Vladimír Kryštof
Cyclin dependent kinases (CDKs) constitute a family of serine/threonine protein kinases that form active complexes with corresponding cyclins to regulate cell cycle transitions and transcription [1]. CDK7 associates with cyclin H and MAT1 to form the CDK-activating kinase (CAK) complex, directing cell cycle transitions by phosphorylating the T-loop of cell cycle CDKs, such as CDK1, 2, 4 and 6 [2,3]. CDK7 is also a component of the general transcription factor IIH (TFIIH), facilitating transcription initiation by phosphorylating the C-terminal domain (CTD) heptapeptide repeats of RNA polymerase II (RNAP II) at Ser5 and Ser7 residues [4,5]. In addition, CDK7 phosphorylates CDK9, a component of positive transcription elongation factor b (P-TEFb), which in turn, phosphorylates the Ser2 residue of the RNAP II CTD to allow productive transcription elongation [6].