Drosophila TFIIA-L is processed into two subunits that are associated with the TBP/TAF complex.

Yokomori, Kyoko; Admon, Arie; Goodrich, James A.; Chen, Jinlong; Tjian, Robert

doi:10.1101/gad.7.11.2235

Cited by 104 publications

(130 citation statements)

References 37 publications

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“…It has been known for quite some time that TFIIA undergoes co-or post-translational cleavage (DeJong and Roeder, 1993;Ma et al, 1993;Yokomori et al, 1993), but neither the cleavage site nor the biological implications of the cleavage have been described. In the present study, we characterised the cleavage site of TFIIAab and shed light on the function of the cleavage.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Cleavage and proteasome-mediated degradation of the basal transcription factor TFIIA

Høiby¹,

Mitsiou²,

Zhou³

et al. 2004

EMBO J

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The transcription factor TFIIA is encoded by two genes, TFIIAab and TFIIAc. In higher eukaryotes, the TFIIAab is translated as a precursor and undergoes proteolytic cleavage; the regulation and biological implications of the cleavage have remained elusive. We determined by Edman degradation that the TFIIAb subunit starts at Asp 278. We found that a cleavage recognition site (CRS), a string of amino acids QVDG at positions À6 to À3 from Asp 278, is essential for cleavage. Mutations in the CRS that prevent cleavage significantly prolong the half-life of TFIIA. Consistently, the cleaved TFIIA is a substrate for the ubiquitin pathway and proteasome-mediated degradation. We show that mutations in the putative phosphorylation sites of TFIIAb greatly affect degradation of the b-subunit. We propose that cleavage and subsequent degradation fine-tune the amount of TFIIA in the cell and consequently the level of transcription.

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Section: Discussionmentioning

confidence: 99%

“…A remarkable phenomenon in higher eukaryotes is the proteolytic cleavage of TFIIAab into TFIIAa and TFIIAb subunits (DeJong and Roeder, 1993;Ma et al, 1993;Yokomori et al, 1993). The site and amino-acid requirements for cleavage have not been described until now, and it is also unclear whether cleavage is a specific and regulated process.…”

Section: Introductionmentioning

confidence: 99%

Cleavage and proteasome-mediated degradation of the basal transcription factor TFIIA

Høiby¹,

Mitsiou²,

Zhou³

et al. 2004

EMBO J

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“…Careful examination of the dHCF sequence revealed no convincing blocks of similarity to the HCF PRO repeat sequence leaving us to conclude that either a variety of unrelated sequences can serve as the substrate for the autocatalytic processing activity or that dHCF is processed through an entirely different mechanism. The 20-and 30-kDa subunits of Drosophila TFIIA are also generated by proteolytic cleavage of a larger precursor, TFIIA-L (Yokomori et al, 1993). The precise cleavage point is not known but can be approximated from the sizes of the processed products.…”

Section: Conservation Of Hcf Processing and Self-association During Mmentioning

confidence: 99%

Molecular cloning of Drosophila HCF reveals proteolytic processing and self‐association of the encoded protein

Mahajan

Johnson

Wilson

2002

Journal Cellular Physiology

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HCF-1 functions as a coactivator for herpes simplex virus VP16 and a number of mammalian transcription factors. Mature HCF-1 is composed of two subunits generated by proteolytic cleavage of a larger precursor at six centrally-located HCF PRO repeats. The resulting N-and Cterminal subunits remain tightly associated via two complementary pairs of self-association domains: termed SAS1N-SAS1C and SAS2N-SAS2C. Additional HCF proteins have been identified in mammals (HCF-2) and Caenorhabditis elegans (CeHCF). Both contain wellconserved SAS1 domains but do not undergo proteolytic processing. Thus, the significance of the cleavage and self-association of HCF-1 remains enigmatic. Here, we describe the isolation of the Drosophila HCF homologue (dHCF) using a genetic screen based on conservation of the SAS1 interaction. The N-terminal β-propeller domain of dHCF supports VP16-induced complex formation and is more similar to mammalian HCF-1 than other homologues. We show that fulllength dHCF expressed in Drosophila cells undergoes proteolytic cleavage giving rise to tightly associated N-and C-terminal subunits. As with HCF-1, the SAS1N and SAS1C elements of dHCF are separated by a large central region, however, this sequence lacks obvious homology to the HCF PRO repeats required for HCF-1 cleavage. The conservation of HCF processing in insect cells argues that formation of separate N-and C-terminal subunits is important for HCF function.HCF-1, also known as C1 factor, is a broadly-expressed nuclear protein involved in the regulation of cellular and viral gene expression. HCF-1 was first identified through its role in transcriptional activation by the herpes simplex virus (HSV) VP16 protein (Gerster and Roeder, 1988;Kristie et al., 1989). Association of HCF-1 with VP16 (also known as α-TIF or Vmw65) leads to the assembly of a multiprotein-DNA complex that includes the POU protein Oct-1 and the TAATGARAT element, a VP16-responsive DNA sequence present in all viral immediate-early (IE) gene promoters (reviewed in (Herr, 1998)). Nuclear localization of VP16 is dependent on association with HCF-1, which contributes a nuclear localization signal (NLS) located at its C-terminus (LaBoissière et al., 1999;Scarr et al., 2000;Wilson et al., 2000). In addition, HCF-1 contains its own activation domain and this is required for optimal transactivation by the VP16-induced complex ( The arrangement of functional domains in human HCF-1 is shown in Figure 1A. HCF-1 is translated as a 230-300-kDa precursor and processed into N-and C-terminal subunits through autocatalytic proteolytic cleavage at a series of six HCF PRO repeats located near the center of the precursor polypeptide (Wilson et al., 1993b;Kristie et al., 1995;Wilson et al., 1995b;Vogel and Kristie, 2000). The resulting subunits remain stably associated via two matched pairs of interaction domains: termed SAS1N-SAS1C and SAS2N-SAS2C . The SAS1C domain corresponds to a pair of fibronectin type 3 (Fn3) repeats, which interact with a 43-residue sequence (SAS1N) that is locate...

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“…In humans and insects these subunits are encoded by the amino-and carboxy-terminal ends of a single large ORF (DeJong and Roeder 1993;Ma et al 1993;Yokomori et al 1993). Although it is unclear whether these subunits arise through proteolytic processing of a larger precursor or by some other mechanism, both subunits remain associated with each other in conjunction with a third subunit encoded by a separate gene.…”

Section: Why Is Hcf Processed!mentioning

confidence: 99%

The HCF repeat is an unusual proteolytic cleavage signal.

Wilson¹,

Peterson²,

Herr³

1995

Genes Dev.

137

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The herpes simplex virus VPl6-associated protein HCF is a nuclear host-cell factor that exists as a family of polypeptides encoded by a single gene. The mature HCF polypeptides are amino-and carboxy-terminal fragments of a large -300-kD precursor protein that arise through cleavage at one or more centrally located sites. The sites of cleavage are the HCF repeats, highly conserved 26-amino-acid sequences repeated six times in the HCF precursor protein. The HCF repeat alone is sufficient to induce cleavage of a heterologous protein, and cleavage occurs at a defined site-PPCEITHET-within the HCF repeat. Alanine-scan mutagenesis was used to identify a large 18-amino-acid segment of the HCF repeat that is important to induce cleavage of a heterologous protein. Even though HCF is cleaved, the majority of amino-and carboxy-terminal cleavage products remain tightly, albeit noncovalently, associated. Modulation of this noncovalent association may provide a mechanism for regulating HCF activity. For example, the cleaved products of an alternative mRNA splicing variant of HCF do not remain associated.

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Drosophila TFIIA-L is processed into two subunits that are associated with the TBP/TAF complex.

Cited by 104 publications

References 37 publications

Cleavage and proteasome-mediated degradation of the basal transcription factor TFIIA

Cleavage and proteasome-mediated degradation of the basal transcription factor TFIIA

Molecular cloning of Drosophila HCF reveals proteolytic processing and self‐association of the encoded protein

The HCF repeat is an unusual proteolytic cleavage signal.

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