057 Understanding the distinct roles of p53 family of transcription factors through identification of protein-protein interactions

Epithelial organs are the first barrier against microorganisms and genotoxic stress, in which the p53 family members p63 and p73 have both overlapping and distinct functions. Intriguingly, p73 displays a very specific localization to basal epithelial cells in human tissues, while p63 is expressed in both basal and differentiated cells. Here, we analyse systematically the literature describing p63 and p73 protein–protein interactions to reveal distinct functions underlying the aforementioned distribution. We have found that p73 and p63 cooperate in the genome stability surveillance in proliferating cells; p73 specific interactors contribute to the transcriptional repression, anaphase promoting complex and spindle assembly checkpoint, whereas p63 specific interactors play roles in the regulation of mRNA processing and splicing in both proliferating and differentiated cells. Our analysis reveals the diversification of the RNA and DNA specific functions within the p53 family.

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Regulation of FoxO transcription factors by acetylation and protein–protein interactions

Biochimica et Biophysica Acta (BBA) - Molecular Cell Research ◽

10.1016/j.bbamcr.2011.03.001 ◽

2011 ◽

Vol 1813 (11) ◽

pp. 1954-1960 ◽

Cited By ~ 155

Author(s):

Hiroaki Daitoku ◽

Jun-ichi Sakamaki ◽

Akiyoshi Fukamizu

Keyword(s):

Transcription Factors ◽

Protein Interactions ◽

Protein Protein Interactions ◽

Foxo Transcription Factors

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In Vivo Quantitative Estimation of DNA-Dependent Interaction of Sox2 and Oct4 Using BirA-Catalyzed Site-Specific Biotinylation

Biomolecules ◽

10.3390/biom10010142 ◽

2020 ◽

Vol 10 (1) ◽

pp. 142 ◽

Cited By ~ 1

Author(s):

Arman Kulyyassov ◽

Vasily Ogryzko

Keyword(s):

Transcription Factors ◽

Protein Interactions ◽

Fluorescent Protein ◽

Quantitative Estimation ◽

Multiple Reaction Monitoring ◽

Negative Control ◽

Protein Protein Interactions ◽

Close Proximity ◽

Green Fluorescent

Protein–protein interactions of core pluripotency transcription factors play an important role during cell reprogramming. Cell identity is controlled by a trio of transcription factors: Sox2, Oct4, and Nanog. Thus, methods that help to quantify protein–protein interactions may be useful for understanding the mechanisms of pluripotency at the molecular level. Here, a detailed protocol for the detection and quantitative analysis of in vivo protein–protein proximity of Sox2 and Oct4 using the proximity-utilizing biotinylation (PUB) method is described. The method is based on the coexpression of two proteins of interest fused to a biotin acceptor peptide (BAP)in one case and a biotin ligase enzyme (BirA) in the other. The proximity between the two proteins leads to more efficient biotinylation of the BAP, which can be either detected by Western blotting or quantified using proteomics approaches, such as a multiple reaction monitoring (MRM) analysis. Coexpression of the fusion proteins BAP-X and BirA-Y revealed strong biotinylation of the target proteins when X and Y were, alternatively, the pluripotency transcription factors Sox2 and Oct4, compared with the negative control where X or Y was green fluorescent protein (GFP), which strongly suggests that Sox2 and Oct4 come in close proximity to each other and interact.

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A yeast library-hybrid assay to screen maize- Rhizoctonia transcription factors and protein-protein interactions in one experimental pipeline

Agri Gene ◽

10.1016/j.aggene.2016.05.002 ◽

2016 ◽

Vol 1 ◽

pp. 15-22 ◽

Cited By ~ 1

Author(s):

Xuan Tang ◽

Junwei Shi ◽

Wubei Dong

Keyword(s):

Transcription Factors ◽

Protein Interactions ◽

Protein Protein Interactions

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Dof DNA-Binding Domains of Plant Transcription Factors Contribute to Multiple Protein-Protein Interactions

European Journal of Biochemistry ◽

10.1111/j.1432-1033.1997.0403a.x ◽

1997 ◽

Vol 250 (2) ◽

pp. 403-410 ◽

Cited By ~ 58

Author(s):

Shuichi Yanagisawa

Keyword(s):

Transcription Factors ◽

Dna Binding ◽

Protein Interactions ◽

Protein Protein Interactions ◽

Dna Binding Domains ◽

Binding Domains ◽

Multiple Protein

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Targeting of the Visna Virus Tat Protein to AP-1 Sites: Interactions with the bZIP Domains of Fos and Jun In Vitro and In Vivo

Journal of Virology ◽

10.1128/jvi.73.1.37-45.1999 ◽

1999 ◽

Vol 73 (1) ◽

pp. 37-45 ◽

Cited By ~ 15

Author(s):

B. A. Morse ◽

L. M. Carruth ◽

J. E. Clements

Keyword(s):

Transcription Factors ◽

Protein Interactions ◽

Tat Protein ◽

Protein Protein Interactions ◽

Viral Promoter ◽

Visna Virus ◽

Cellular Transcription ◽

Virus Promoter

ABSTRACT The visna virus Tat protein is required for efficient viral transcription from the visna virus long terminal repeat (LTR). AP-1 sites within the visna virus LTR, which can be bound by the cellular transcription factors Fos and Jun, are also necessary for Tat-mediated transcriptional activation. A potential mechanism by which the visna virus Tat protein could target the viral promoter is by protein-protein interactions with Fos and/or Jun bound to AP-1 sites in the visna virus LTR. Once targeted to the visna virus promoter, the Tat protein could then interact with basal transcription factors to activate transcription. To examine protein-protein interactions with cellular proteins at the visna virus promoter, we used an in vitro protein affinity chromatography assay and electrophoretic mobility shift assay, in addition to an in vivo two-hybrid assay, to show that the visna virus Tat protein specifically interacts with the cellular transcription factors Fos and Jun and the basal transcription factor TBP (TATA binding protein). The Tat domain responsible for interactions with Fos and Jun was localized to an alpha-helical domain within amino acids 34 to 69 of the protein. The TBP binding domain was localized to amino acids 1 to 38 of Tat, a region previously described by our laboratory as the visna virus Tat activation domain. The bZIP domains of Fos and Jun were found to be important for the interactions with Tat. Mutations within the basic domains of Fos and Jun abrogated binding to Tat in the in vitro assays. The visna virus Tat protein was also able to interact with covalently cross-linked Fos and Jun dimers. Thus, the visna virus Tat protein appears to target AP-1 sites in the viral promoter in a mechanism similar to the interaction of human T-cell leukemia virus type 1 Tax with the cellular transcription factor CREB, by binding the basic domains of an intact bZIP dimer. The association between Tat, Fos, and Jun would position Tat proximal to the viral TATA box, where the visna virus Tat activation domain could contact TBP to activate viral transcription.

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ApicoTFdb: the comprehensive web repository of apicomplexan transcription factors and transcription-associated co-factors

Database ◽

10.1093/database/baz094 ◽

2019 ◽

Vol 2019 ◽

Author(s):

Rahila Sardar ◽

Abhinav Kaushik ◽

Rajan Pandey ◽

Asif Mohmmed ◽

Shakir Ali ◽

...

Keyword(s):

Transcription Factors ◽

Protein Interactions ◽

Drug Targets ◽

Complex Life Cycle ◽

Protein Protein Interactions ◽

Apicomplexan Parasites ◽

Reference Protein ◽

Ap2 Family ◽

Novel Drug ◽

Novel Drug Targets

Abstract Despite significant progress in apicomplexan genome sequencing and genomics, the current list of experimentally validated transcription factors (TFs) in these genomes is incomplete and mainly consists of AP2 family of proteins, with only a limited number of non-AP2 family TFs and transcription-associated co-factors (TcoFs). We have performed a systematic bioinformatics-aided prediction of TFs and TcoFs in apicomplexan genomes and developed the ApicoTFdb database which consists of experimentally validated as well as computationally predicted TFs and TcoFs in 14 apicomplexan species. The predicted TFs are manually curated to complement the existing annotations. The current version of the database includes 1292 TFs which includes experimentally validated and computationally predicted TFs, representing 20 distinct families across 14 apicomplexan species. The predictions include TFs of TUB, NAC, BSD, HTH, Cupin/Jumonji, winged helix and FHA family proteins, not reported earlier as TFs in the genomes. Apart from TFs, ApicoTFdb also classifies TcoFs into three main subclasses: TRs, CRRs and RNARs, representing 2491 TcoFs in 14 apicomplexan species, are analyzed in this study. The database is designed to integrate different tools for comparative analysis. All entries in the database are dynamically linked with other databases, literature reference, protein–protein interactions, pathways and annotations associated with each protein. ApicoTFdb will be useful to the researchers interested in less-studied gene regulatory mechanisms mediating the complex life cycle of the apicomplexan parasites. The database will aid in the discovery of novel drug targets to much needed combat the growing drug resistance in the parasites.

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The transcription factors Elk-1 and serum response factor interact by direct protein-protein contacts mediated by a short region of Elk-1.

Molecular and Cellular Biology ◽

10.1128/mcb.14.5.3283 ◽

1994 ◽

Vol 14 (5) ◽

pp. 3283-3291 ◽

Cited By ~ 103

Author(s):

P Shore ◽

A D Sharrocks

Keyword(s):

Transcription Factor ◽

Transcription Factors ◽

Protein Interactions ◽

Serum Response Factor ◽

Specific Protein ◽

Response Factor ◽

Protein Protein Interactions ◽

Amino Acid Peptide ◽

Necessary And Sufficient ◽

Serum Response

Transcriptional induction of the c-fos gene in response to epidermal growth factor stimulation is mediated in part by a ternary nucleoprotein complex within the promoter consisting of serum response factor (SRF), p62TCF/Elk-1 and the serum response element (SRE). Both SRF and p62TCF/Elk-1 contact the DNA and bind in a cooperative manner to the SRE. In this study, we demonstrate that SRF and Elk-1 interact directly in the absence of the SRE. A 30-amino-acid peptide from Elk-1 (B-box) is both necessary and sufficient to mediate protein-protein contacts with SRF. Moreover, the Elk-1 B-box is necessary to enable SRF-dependent binding of an alternative ETS domain (from the transcription factor PU.1) to the c-fos SRE. Mutations in either the Elk-1 B-box or the C-terminal half of the SRF DNA-binding domain (coreSRF) which show reduced ability to form ternary complexes also show greatly reduced protein-protein interactions in the absence of the SRE. Our results clearly demonstrate that direct protein-protein interactions between the transcription factors Elk-1 and SRF, in addition to DNA contacts, contribute to the formation of a ternary complex on the c-fos SRE. We discuss the wider applicability of our results in describing specific protein-protein interactions between short well-defined transcription factor domains.

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