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Structure-function analysis indicates that sumoylation modulates DNA-binding activity of STAT1

Tutkimustuotosvertaisarvioitu

Standard

Structure-function analysis indicates that sumoylation modulates DNA-binding activity of STAT1. / Grönholm, Juha; Vanhatupa, Sari; Ungureanu, Daniela; Väliaho, Jouni; Laitinen, Tuomo; Valjakka, Jarkko; Silvennoinen, Olli.

julkaisussa: BMC BIOCHEMISTRY, Vuosikerta 13, Nro 1, 20, 2012.

Tutkimustuotosvertaisarvioitu

Harvard

Grönholm, J, Vanhatupa, S, Ungureanu, D, Väliaho, J, Laitinen, T, Valjakka, J & Silvennoinen, O 2012, 'Structure-function analysis indicates that sumoylation modulates DNA-binding activity of STAT1', BMC BIOCHEMISTRY, Vuosikerta. 13, Nro 1, 20. https://doi.org/10.1186/1471-2091-13-20

APA

Grönholm, J., Vanhatupa, S., Ungureanu, D., Väliaho, J., Laitinen, T., Valjakka, J., & Silvennoinen, O. (2012). Structure-function analysis indicates that sumoylation modulates DNA-binding activity of STAT1. BMC BIOCHEMISTRY, 13(1), [20]. https://doi.org/10.1186/1471-2091-13-20

Vancouver

Grönholm J, Vanhatupa S, Ungureanu D, Väliaho J, Laitinen T, Valjakka J et al. Structure-function analysis indicates that sumoylation modulates DNA-binding activity of STAT1. BMC BIOCHEMISTRY. 2012;13(1). 20. https://doi.org/10.1186/1471-2091-13-20

Author

Grönholm, Juha ; Vanhatupa, Sari ; Ungureanu, Daniela ; Väliaho, Jouni ; Laitinen, Tuomo ; Valjakka, Jarkko ; Silvennoinen, Olli. / Structure-function analysis indicates that sumoylation modulates DNA-binding activity of STAT1. Julkaisussa: BMC BIOCHEMISTRY. 2012 ; Vuosikerta 13, Nro 1.

Bibtex - Lataa

@article{17122291a252487d9f3cc45eb1ee9e78,
title = "Structure-function analysis indicates that sumoylation modulates DNA-binding activity of STAT1",
abstract = "Background: STAT1 is an essential transcription factor for interferon-γ-mediated gene responses. A distinct sumoylation consensus site (ψKxE) 702IKTE705 is localized in the C-terminal region of STAT1, where Lys703 is a target for PIAS-induced SUMO modification. Several studies indicate that sumoylation has an inhibitory role on STAT1-mediated gene expression but the molecular mechanisms are not fully understood. Results: Here, we have performed a structural and functional analysis of sumoylation in STAT1. We show that deconjugation of SUMO by SENP1 enhances the transcriptional activity of STAT1, confirming a negative regulatory effect of sumoylation on STAT1 activity. Inspection of molecular model indicated that consensus site is well exposed to SUMO-conjugation in STAT1 homodimer and that the conjugated SUMO moiety is directed towards DNA, thus able to form a sterical hindrance affecting promoter binding of dimeric STAT1. In addition, oligoprecipitation experiments indicated that sumoylation deficient STAT1 E705Q mutant has higher DNA-binding activity on STAT1 responsive gene promoters than wild-type STAT1. Furthermore, sumoylation deficient STAT1 E705Q mutant displayed enhanced histone H4 acetylation on interferon-γ- responsive promoter compared to wild-type STAT1. Conclusions: Our results suggest that sumoylation participates in regulation of STAT1 responses by modulating DNA-binding properties of STAT1.",
keywords = "Interferon, Signal transducers and activators of transcription (STATs), Signal transduction, Sumoylation, Transcription factors",
author = "Juha Gr{\"o}nholm and Sari Vanhatupa and Daniela Ungureanu and Jouni V{\"a}liaho and Tuomo Laitinen and Jarkko Valjakka and Olli Silvennoinen",
year = "2012",
doi = "10.1186/1471-2091-13-20",
language = "English",
volume = "13",
journal = "BMC BIOCHEMISTRY",
number = "1",

}

RIS (suitable for import to EndNote) - Lataa

TY - JOUR

T1 - Structure-function analysis indicates that sumoylation modulates DNA-binding activity of STAT1

AU - Grönholm, Juha

AU - Vanhatupa, Sari

AU - Ungureanu, Daniela

AU - Väliaho, Jouni

AU - Laitinen, Tuomo

AU - Valjakka, Jarkko

AU - Silvennoinen, Olli

PY - 2012

Y1 - 2012

N2 - Background: STAT1 is an essential transcription factor for interferon-γ-mediated gene responses. A distinct sumoylation consensus site (ψKxE) 702IKTE705 is localized in the C-terminal region of STAT1, where Lys703 is a target for PIAS-induced SUMO modification. Several studies indicate that sumoylation has an inhibitory role on STAT1-mediated gene expression but the molecular mechanisms are not fully understood. Results: Here, we have performed a structural and functional analysis of sumoylation in STAT1. We show that deconjugation of SUMO by SENP1 enhances the transcriptional activity of STAT1, confirming a negative regulatory effect of sumoylation on STAT1 activity. Inspection of molecular model indicated that consensus site is well exposed to SUMO-conjugation in STAT1 homodimer and that the conjugated SUMO moiety is directed towards DNA, thus able to form a sterical hindrance affecting promoter binding of dimeric STAT1. In addition, oligoprecipitation experiments indicated that sumoylation deficient STAT1 E705Q mutant has higher DNA-binding activity on STAT1 responsive gene promoters than wild-type STAT1. Furthermore, sumoylation deficient STAT1 E705Q mutant displayed enhanced histone H4 acetylation on interferon-γ- responsive promoter compared to wild-type STAT1. Conclusions: Our results suggest that sumoylation participates in regulation of STAT1 responses by modulating DNA-binding properties of STAT1.

AB - Background: STAT1 is an essential transcription factor for interferon-γ-mediated gene responses. A distinct sumoylation consensus site (ψKxE) 702IKTE705 is localized in the C-terminal region of STAT1, where Lys703 is a target for PIAS-induced SUMO modification. Several studies indicate that sumoylation has an inhibitory role on STAT1-mediated gene expression but the molecular mechanisms are not fully understood. Results: Here, we have performed a structural and functional analysis of sumoylation in STAT1. We show that deconjugation of SUMO by SENP1 enhances the transcriptional activity of STAT1, confirming a negative regulatory effect of sumoylation on STAT1 activity. Inspection of molecular model indicated that consensus site is well exposed to SUMO-conjugation in STAT1 homodimer and that the conjugated SUMO moiety is directed towards DNA, thus able to form a sterical hindrance affecting promoter binding of dimeric STAT1. In addition, oligoprecipitation experiments indicated that sumoylation deficient STAT1 E705Q mutant has higher DNA-binding activity on STAT1 responsive gene promoters than wild-type STAT1. Furthermore, sumoylation deficient STAT1 E705Q mutant displayed enhanced histone H4 acetylation on interferon-γ- responsive promoter compared to wild-type STAT1. Conclusions: Our results suggest that sumoylation participates in regulation of STAT1 responses by modulating DNA-binding properties of STAT1.

KW - Interferon

KW - Signal transducers and activators of transcription (STATs)

KW - Signal transduction

KW - Sumoylation

KW - Transcription factors

UR - http://www.scopus.com/inward/record.url?scp=84871785836&partnerID=8YFLogxK

U2 - 10.1186/1471-2091-13-20

DO - 10.1186/1471-2091-13-20

M3 - Article

VL - 13

JO - BMC BIOCHEMISTRY

JF - BMC BIOCHEMISTRY

IS - 1

M1 - 20

ER -