Dynamic regulation of pol II transcription by the mammalian Mediator complex

Malik, Sohail; Roeder, Robert G.

doi:10.1016/j.tibs.2005.03.009

Cited by 347 publications

(363 citation statements)

References 81 publications

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“…Third, biochemical studies have revealed that CDK8 is the only enzymatic subunit of the transcription cofactor complex called Mediator complex, which bridges specific transcription factors and the general transcription machinery. [9][10][11][12][13] Mediator complex is composed of up to 30 different subunits, most of which are well conserved in eukaryotes. 10,14,15 It is proposed that the Mediator complex is involved in most, if not all, of the RNA polymerase II-mediated transcription.…”

Section: Tumor-suppressive Effects Of Cdk8 In Endometrial Cancer Cellsmentioning

confidence: 99%

Tumor-suppressive effects of CDK8 in endometrial cancer cells

Wang

et al. 2013

Cell Cycle

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Section: Tumor-suppressive Effects Of Cdk8 In Endometrial Cancer Cellsmentioning

confidence: 99%

Tumor-suppressive effects of CDK8 in endometrial cancer cells

Wang

et al. 2013

Cell Cycle

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“…The MDT-15 proteins exhibit sequence similarity to yeast MED15/ GAL11 (subsequently named GAL11) ) and human MED15/ARC105/TIG-1/PCQAP proteins (subsequently named MED15) ). GAL11 and MED15 proteins are subunits of the yeast and human Mediator complexes, respectively, multisubunit protein complexes that act as transcriptional coregulators for regulatory factors (Blazek et al 2005;Malik and Roeder 2005).…”

Section: Specific Interaction Between Nhr-49 and Mdt-15mentioning

confidence: 99%

A Mediator subunit, MDT-15, integrates regulation of fatty acid metabolism by NHR-49-dependent and -independent pathways inC. elegans

Taubert¹,

Gilst²,

Hansen³

et al. 2006

Genes Dev.

232

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“…Med25 consists of two domains, the activator interaction domain (ACID) 24 that binds the VP16 TAD, and a 'von Willebrand factor type A' domain that anchors Med25 to Mediator 24 . Mediator generally conveys regulatory information by forming a bridge between activators and the basal Pol II machinery 28,29 . Whereas information on the core Mediator structure is emerging, structural information about its more peripheral activator-binding domains is limited to the KIX domain in subunit Med15 (or Arc105) 30,31 .…”

mentioning

confidence: 99%

Structure and VP16 binding of the Mediator Med25 activator interaction domain

Vojnic

Mourão

Seizl

et al. 2011

Nat Struct Mol Biol

111

161

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4 0 4 VOLUME 18 NUMBER 4 APRIL 2011 nAture structurAl & moleculAr biologyActivator proteins regulate eukaryotic RNA polymerase II (Pol II) transcription in response to developmental and environmental signals. They bind to the DNA recognition sites of target genes with a sequence-specific DNA-binding domain, and recruit components of the Pol II machinery through a transcriptional activation domain (TAD) 1,2 . Activators have been classified as acidic, glutamine-rich, proline-rich and serine/threonine-rich, depending on the preponderance of amino acids in their TAD 3 . An archetypal acidic activator is the herpes simplex virus protein 16 (VP16), which activates the expression of immediate early viral genes during infection 4-8 . VP16 exerts its activating function through a C-terminal TAD that includes residues 413-490 (refs. 9-13). The VP16 TAD has been intensely used for studying transcriptional activation. Usually, the VP16 TAD is fused with its N terminus to the DNA-binding domain of the yeast transcription factor Gal4. The resulting Gal4-VP16 activator fusion protein stimulates transcription from promoters that contain Gal4-binding sites in the yeast and mammalian transcription systems in vivo 14,15 and in vitro 16,17 . This indicates that basic mechanisms of transcription activation are conserved amongst eukaryotes. The VP16 TAD targets basal Pol II transcription factors, including TFIIA, TFIIB, TFIID, the TFIIH subunit Tfb1/p62 (yeast/human) and the Mediator co-activator [18][19][20][21][22][23] . The VP16 TAD binds the Mediator subunit Med25 (also called Arc92) [24][25][26][27] , which is specific to higher eukaryotes. Med25 consists of two domains, the activator interaction domain (ACID) 24 that binds the VP16 TAD, and a 'von Willebrand factor type A' domain that anchors Med25 to Mediator 24 . Mediator generally conveys regulatory information by forming a bridge between activators and the basal Pol II machinery 28,29 . Whereas information on the core Mediator structure is emerging, structural information about its more peripheral activator-binding domains is limited to the KIX domain in subunit Med15 (or Arc105) 30,31 .The VP16 TAD is intrinsically flexible, whereas the VP16 core domain (residues 49-402) forms a stable structure 23,[32][33][34] . The TAD contains two functional subdomains, H1 (residues 410-452) and H2 (residues 453-490), which activate transcription independently 35,36 . Both H1 and H2 contain acidic amino acids, but specific bulky hydrophobic and aromatic residues are required for their function [36][37][38][39] . H2 has been proposed to adopt an α-helical conformation when bound to TFIIB 40 . NMR analysis revealed a nine-residue amphipathic α-helix in H2 that docks onto a PH fold in Tfb1 21 . On the basis of these and other results it is assumed that acidic TADs are flexible in their free state, but become transiently structured upon interaction with their target proteins.Here we report the NMR structure of the Mediator Med25 ACID and analyze its structural and functional interaction wi...

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Dynamic regulation of pol II transcription by the mammalian Mediator complex

Cited by 347 publications

References 81 publications

Tumor-suppressive effects of CDK8 in endometrial cancer cells

Tumor-suppressive effects of CDK8 in endometrial cancer cells

A Mediator subunit, MDT-15, integrates regulation of fatty acid metabolism by NHR-49-dependent and -independent pathways inC. elegans

Structure and VP16 binding of the Mediator Med25 activator interaction domain

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