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Hermann, Stefan
Publications (4 of 4) Show all publications
Ferreira, M. E., Hermann, S., Prochasson, P., Workman, J. L., Berndt, K. D. & Wright, A. P. (2005). Mechanism of transcription factor recruitment by acidic activators. Journal of Biological Chemistry, 280(23), 21779-21784
Open this publication in new window or tab >>Mechanism of transcription factor recruitment by acidic activators
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2005 (English)In: Journal of Biological Chemistry, ISSN 0021-9258, E-ISSN 1083-351X, Vol. 280, no 23, p. 21779-21784Article in journal (Refereed) Published
Abstract [en]

Many transcriptional activators are intrinsically unstructured yet display unique, defined conformations when bound to target proteins. Target-induced folding provides a mechanism by which activators could form specific interactions with an array of structurally unrelated target proteins. Evidence for such a binding mechanism has been reported previously in the context of the interaction between the cancer-related c-Myc protein and the TATA-binding protein, which can be modeled as a two-step process in which a rapidly forming, low affinity complex slowly converts to a more stable form, consistent with a coupled binding and folding reaction. To test the generality of the target-induced folding model, we investigated the binding of two widely studied acidic activators, Gal4 and VP16, to a set of target proteins, including TATA-binding protein and the Swi1 and Snf5 subunits of the Swi/Snf chromatin remodeling complex. Using surface plasmon resonance, we show that these activator-target combinations also display bi-phasic kinetics suggesting two distinct steps. A fast initial binding phase that is inhibited by high ionic strength is followed by a slow phase that is favored by increased temperature. In all cases, overall affinity increases with temperature and, in most cases, with increased ionic strength. These results are consistent with a general mechanism for recruitment of transcriptional components to promoters by naturally occurring acidic activators, by which the initial contact is mediated predominantly through electrostatic interactions, whereas subsequent target-induced folding of the activator results in a stable complex.

National Category
Biochemistry and Molecular Biology
Identifiers
urn:nbn:se:sh:diva-14456 (URN)10.1074/jbc.M502627200 (DOI)000229557900015 ()15826952 (PubMedID)2-s2.0-20444475372 (Scopus ID)
Available from: 2011-12-23 Created: 2011-12-23 Last updated: 2017-12-08Bibliographically approved
Cunnea, P. M., Miranda-Vizuete, A., Bertoli, G., Simmen, T., Damdimopoulos, A. E., Hermann, S., . . . Spyrou, G. (2003). ERdJ5, an endoplasmic reticulum (ER)-resident protein containing DnaJ and thioredoxin domains, is expressed in secretory cells or following ER stress. Journal of Biological Chemistry, 278(2), 1059-1066
Open this publication in new window or tab >>ERdJ5, an endoplasmic reticulum (ER)-resident protein containing DnaJ and thioredoxin domains, is expressed in secretory cells or following ER stress
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2003 (English)In: Journal of Biological Chemistry, ISSN 0021-9258, E-ISSN 1083-351X, Vol. 278, no 2, p. 1059-1066Article in journal (Refereed) Published
National Category
Biochemistry and Molecular Biology
Identifiers
urn:nbn:se:sh:diva-15591 (URN)10.1074/jbc.M206995200 (DOI)000180321900049 ()12411443 (PubMedID)2-s2.0-0037428470 (Scopus ID)
Available from: 2012-02-22 Created: 2012-02-21 Last updated: 2017-12-07Bibliographically approved
Flinn, E. M., Wallberg, A. E., Hermann, S., Grant, P. A., Workman, J. L. & Wright, A. P. (2002). Recruitment of Gen5-containing complexes during c-Myc-dependent gene activation - Structure and function aspects. Journal of Biological Chemistry, 277(26), 23399-23406
Open this publication in new window or tab >>Recruitment of Gen5-containing complexes during c-Myc-dependent gene activation - Structure and function aspects
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2002 (English)In: Journal of Biological Chemistry, ISSN 0021-9258, E-ISSN 1083-351X, Vol. 277, no 26, p. 23399-23406Article in journal (Refereed) Published
Abstract [en]

The N-terminal domain of c-Myc plays a key role in cellular transformation and is involved in both activation and repression of target genes as well as in modulated proteolysis of c-Myc via the proteasome. Given this functional complexity, it has been difficult to clarify the structures within the N terminus that contribute to these different processes as well as the mechanisms by which they function. We have used a simplified yeast model system to identify the primary determinants within the N terminus for W chromatin remodeling of a promoter, (ii) gene activation from a chromatin template in vivo, and (iii) interaction with highly purified Gcn5 complexes as well as other chromatin-remodeling complexes in vitro. The results identify two regions that contain autonomous chromatin opening and gene activation activity, but both regions are required for efficient interaction with chromatin-remodeling complexes in vitro. The conserved Myc boxes do not play a direct role in gene activation, and Myc box II is not generally required for in vitro interactions with remodeling complexes. The yeast SAGA complex, which is orthologous to the human GCN5-TRRAP complex that interacts with Myc in human cells, plays a role in Myc-mediated chromatin opening at the promoter but may also be involved in later steps of gene activation.

National Category
Biochemistry and Molecular Biology
Identifiers
urn:nbn:se:sh:diva-15799 (URN)10.1074/jbc.M201704200 (DOI)000176475700040 ()11973336 (PubMedID)2-s2.0-0037189508 (Scopus ID)
Available from: 2012-03-08 Created: 2012-03-07 Last updated: 2017-12-07Bibliographically approved
Hermann, S., Berndt, K. D. & Wright, A. P. (2001). How transcriptional activators bind target proteins. Journal of Biological Chemistry, 276(43), 40127-40132
Open this publication in new window or tab >>How transcriptional activators bind target proteins
2001 (English)In: Journal of Biological Chemistry, ISSN 0021-9258, E-ISSN 1083-351X, Vol. 276, no 43, p. 40127-40132Article in journal (Refereed) Published
Abstract [en]

The product of the proto-oncogene c-myc influences many cellular processes through the regulation of specific target genes. Through its transactivation domain (TAD), c-Myc protein interacts with several transcription factors, including TATA-binding protein (TBP). We present data that suggest that in contrast to some other transcriptional activators, an extended length of the c-Myc TAD is required for its binding to TBP. Our data also show that this interaction is a multistep process, in which a rapidly forming low affinity complex slowly converts to a more stable form. The initial complex formation results from ionic or polar interactions, whereas the slow conversion to a more stable form is hydrophobic in nature. Based on our results, we suggest two alternative models for activation domain/target protein interactions, which together provide a single universal paradigm for understanding activator-target factor interactions.

National Category
Biochemistry and Molecular Biology
Identifiers
urn:nbn:se:sh:diva-15842 (URN)10.1074/jbc.M103793200 (DOI)000171789200084 ()11514548 (PubMedID)2-s2.0-0035955635 (Scopus ID)
Available from: 2012-03-12 Created: 2012-03-09 Last updated: 2017-12-07Bibliographically approved
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