A transcription reinitiation intermediate that is stabilized by activator

Yudkovsky, Natalya; Ranish, Jeffrey A.; Hahn, Steven

doi:10.1038/35041603

Cited by 360 publications

(386 citation statements)

References 27 publications

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“…This finding suggests that CR3 may function in part by holding the Mediator at the promoter following each round of transcription initiation and the required disassembly of the PIC. This mechanism has been suggested to stimulate the rate of transcription reinitiation by the strong VP16 AD (Yudkovsky et al, 2000). In addition, the studies with ELK1 suggest that an interaction with MED23 stimulates PIC initiation.…”

Section: E1a Conserved Region 3 Activation Of Early Viral Gene Expresmentioning

confidence: 94%

Recent lessons in gene expression, cell cycle control, and cell biology from adenovirus

2005

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Adenovirus continues to be an important model system for investigating basic aspects of cell biology. Interactions of several cellular proteins with E1A conserved regions (CR) 1 and 2, and inhibition of apoptosis by E1B proteins are required for oncogenic transformation. CR2 binds RB family members, de-repressing E2F transcription factors, thus activating genes required for cell cycling. E1B-19K is a BCL2 homolog that binds and inactivates proapoptotic BAK and BAX. E1B-55K binds p53, inhibiting its transcriptional activation function. In productively infected cells, E1B-55K and E4orf6 assemble a ubiquitin ligase with cellular proteins Elongins B and C, Cullin 5 and RBX1 that polyubiquitinates p53 and one or more subunits of the MRN complex involved in DNA doublestrand break repair, directing them to proteosomal degradation. E1A CR3 activates viral transcription by interacting with the MED23 Mediator subunit, stimulating preinitiation complex assembly on early viral promoters and probably also the rate at which they initiate transcription. The viral E1B-55K/E4orf6 ubiquitin ligase is also required for efficient viral late protein synthesis in many cell types, but the mechanism is not understood. E1A CR1 binds several chromatin-modifying complexes, but how this contributes to stimulation of cellular DNA synthesis and transformation is not clear. E1A CR4 binds the CtBP corepressor, but the mechanism by which this modulates the frequency of transformation remains to be determined. Clearly, adenovirus has much left to teach us about fundamental cellular processes.

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Section: E1a Conserved Region 3 Activation Of Early Viral Gene Expresmentioning

confidence: 94%

Recent lessons in gene expression, cell cycle control, and cell biology from adenovirus

2005

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“…High-resolution crystal structures have elucidated the TFIIB-TBP-DNA and RNAP II complexes, but little is known about TFIIB before it is incorporated into this complex (Hampsey, 1998;Hahn, 2004). It is thought that with each round of transcription TFIIB does not remain bound to the promoter, suggesting that the study of the import of new TFIIB may be relevant to transcription (Yudkovsky et al, 2000). Here we identify the import pathway of Sua7p, the yeast version of TFIIB.…”

Section: Introductionmentioning

confidence: 94%

Nuclear Import of TFIIB Is Mediated by Kap114p, a Karyopherin with Multiple Cargo-binding Domains

Hodges

Leslie

Mosammaparast

et al. 2005

MBoC

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Nuclear import and export is mediated by an evolutionarily conserved family of soluble transport factors, the karyopherins (referred to as importins and exportins). The yeast karyopherin Kap114p has previously been shown to import histones H2A and H2B, Nap1p, and a component of the preinitiation complex (PIC), TBP. Using a proteomic approach, we have identified several potentially new cargoes for Kap114p. These cargoes include another PIC component, the general transcription factor IIB or Sua7p, which interacted directly with Kap114p. Consistent with its role as a Sua7p import factor, deletion of KAP114 led to specific mislocalization of Sua7p to the cytoplasm. An interaction between Sua7p and TBP was also detected in cytosol, raising the possibility that both Sua7p and TBP can be coimported by Kap114p. We have also shown that Kap114p possesses multiple overlapping binding sites for its partners, Sua7p, Nap1p, and H2A and H2B, as well as RanGTP and nucleoporins. In addition, we have assembled an in vitro complex containing Sua7p, Nap1p, and histones H2A and H2B, suggesting that this Kap may import several proteins simultaneously. The import of more than one cargo at a time would increase the efficiency of each import cycle and may allow the regulation of coimported cargoes. INTRODUCTIONIn eukaryotic cells the nucleocytoplasmic transport of most proteins and some RNAs is mediated by an evolutionarily conserved family of soluble transport factors, the karyopherins (also referred to as importins and exportins; reviewed in Weis, 2003;Harel and Forbes, 2004;Mosammaparast and Pemberton, 2004). After synthesis in the cytoplasm, most nuclear protein cargoes are bound by a member of the karyopherin family, through direct interaction with a nuclear localization sequence contained in the cargo protein. Transport through the nuclear pore complex occurs via transient interactions of the karyopherin with the NPC. Once in the nucleus, the karyopherin encounters a high concentration of RanGTP, which acts as a regulator of transport. Interaction of the karyopherin with RanGTP leads to dissociation of the karyopherin from its nuclear cargo (Weis, 2003;Harel and Forbes, 2004;Mosammaparast and Pemberton, 2004). In some circumstances, nuclear-binding partners of the cargo appear to also play a role in stimulating the dissociation of Kap and cargo (Senger et al., 1998;Lee and Aitchison, 1999;Pemberton et al., 1999). In yeast, there are 14 members of the karyopherin family, with Ͼ20 members in mammalian cells (Mosammaparast and Pemberton, 2004). Karyopherins appear to function in either nuclear import or nuclear export, with only two examples of a Kap that works in both directions (Weis, 2003;Harel and Forbes, 2004;Mosammaparast and Pemberton, 2004). In yeast, 11 members of the karyopherin family must import at least 1500 nuclear proteins, suggesting that each receptor must have many cargoes. To date specific transport receptor-cargo pairs have only been shown for ϳ30 cargoes; in addition the NLS sequences recognized by most Kaps is n...

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“…Previously it was shown that PIC assembly occurs in at least three stages in this in vitro system, with TFIID and TFIIA recruited first to the promoter; TFIIB, Pol II, TFIIF, Mediator, and TFIIE recruited cooperatively in the next step; and TFIIH binding last (Ranish et al 1999;Yudkovsky et al 2000). PICs were assembled on immobilized templates by using ex- Interactions among SAGA, TFIIA, and TBP tracts containing conditional mutations in TBP, TFIIB, Mediator, or TFIIH (Fig.…”

Section: Identification Of Polypeptides That Cross-link To the Tfiia Ntdmentioning

confidence: 99%

Positive and negative functions of the SAGA complex mediated through interaction of Spt8 with TBP and the N-terminal domain of TFIIA

Warfield

Ranish²,

Hahn³

2004

Genes Dev.

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A surface that is required for rapid formation of preinitiation complexes (PICs) was identified on the N-terminal domain (NTD) of the RNA Pol II general transcription factor TFIIA. Site-specific photocross-linkers and tethered protein cleavage reagents positioned on the NTD of TFIIA and assembled in PICs identified the SAGA subunit Spt8 and the TFIID subunit Taf4 as located near this surface. In agreement with these findings, mutations in Spt8 and the TFIIA NTD interact genetically. Using purified proteins, it was found that TFIIA and Spt8 do not stably bind to each other, but rather both compete for binding to TBP. Consistent with this competition, Spt8 inhibits the binding of SAGA to PICs in the absence of activator. In the presence of activator, Spt8 enhances transcription in vitro, and the positive function of the TFIIA NTD is largely mediated through Spt8. Our results suggest a mechanism for the previously observed positive and negative effects of Spt8 on transcription observed in vivo.[Keywords: Transcription; SAGA; TFIIA; coactivator; repression] Supplemental material is available at http://www.genesdev.org.

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A transcription reinitiation intermediate that is stabilized by activator

Cited by 360 publications

References 27 publications

Recent lessons in gene expression, cell cycle control, and cell biology from adenovirus

Recent lessons in gene expression, cell cycle control, and cell biology from adenovirus

Nuclear Import of TFIIB Is Mediated by Kap114p, a Karyopherin with Multiple Cargo-binding Domains

Positive and negative functions of the SAGA complex mediated through interaction of Spt8 with TBP and the N-terminal domain of TFIIA

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