Proteasomal activity modulates TGF-β signaling in a gene-specific manner

Fan Zhang; Mia Mönkkönen; Stina Roth; Marikki Laiho

doi:10.1016/S0014-5793(02)03163-0

Proteasomal activity modulates TGF-β signaling in a gene-specific manner

Fan Zhang, Mia Mönkkönen, Stina Roth, Marikki Laiho

Research output: Contribution to journal › Article › peer-review

15 Scopus citations

Abstract

Transforming growth factor-β (TGF-β) signaling relies on Smad-signaling pathway controlled in part by the proteasome. Here we demonstrate that inhibition of the proteasome function in mink epithelial cells accumulates both positive and negative modulators of TGF-β signaling, phospho-Smad2 and SnoN. Inhibition of the proteasome led to abrogation of TGF-β target gene regulation in a gene-specific manner. While regulation of p15Ink4b and myc by TGF-β are lost, PAI-1 induction, previously shown to occur in a Smad3-dependent manner, was not affected by treatment of the cells with the proteasomal inhibitor MG132. The results suggest that proteasomal activity is required for TGF-β signaling in a gene-specific manner.

Original language	English (US)
Pages (from-to)	58-62
Number of pages	5
Journal	FEBS Letters
Volume	527
Issue number	1-3
DOIs	https://doi.org/10.1016/S0014-5793(02)03163-0
State	Published - Sep 11 2002
Externally published	Yes

Keywords

Proteasome
Signaling
Smad
SnoN
Transforming growth factor-β

ASJC Scopus subject areas

Biophysics
Structural Biology
Biochemistry
Molecular Biology
Genetics
Cell Biology

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10.1016/S0014-5793(02)03163-0

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title = "Proteasomal activity modulates TGF-β signaling in a gene-specific manner",

abstract = "Transforming growth factor-β (TGF-β) signaling relies on Smad-signaling pathway controlled in part by the proteasome. Here we demonstrate that inhibition of the proteasome function in mink epithelial cells accumulates both positive and negative modulators of TGF-β signaling, phospho-Smad2 and SnoN. Inhibition of the proteasome led to abrogation of TGF-β target gene regulation in a gene-specific manner. While regulation of p15Ink4b and myc by TGF-β are lost, PAI-1 induction, previously shown to occur in a Smad3-dependent manner, was not affected by treatment of the cells with the proteasomal inhibitor MG132. The results suggest that proteasomal activity is required for TGF-β signaling in a gene-specific manner.",

keywords = "Proteasome, Signaling, Smad, SnoN, Transforming growth factor-β",

author = "Fan Zhang and Mia M{\"o}nkk{\"o}nen and Stina Roth and Marikki Laiho",

note = "Funding Information: This work was supported by the Academy of Finland grants 32788 (M.L.) and 44885 (Finnish Centre of Excellence Program 2000-2005), the University of Helsinki, Biocentrum Helsinki, Sigrid Juselius Foundation, the Finnish Cancer Foundation and HUCH EVO grants. We thank Ms. Virpi P{\"a}ivinen and Ms. Maija H{\"a}likk{\"a} for excellent technical assistance.",

year = "2002",

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day = "11",

doi = "10.1016/S0014-5793(02)03163-0",

language = "English (US)",

volume = "527",

pages = "58--62",

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T1 - Proteasomal activity modulates TGF-β signaling in a gene-specific manner

AU - Zhang, Fan

AU - Mönkkönen, Mia

AU - Roth, Stina

AU - Laiho, Marikki

N1 - Funding Information: This work was supported by the Academy of Finland grants 32788 (M.L.) and 44885 (Finnish Centre of Excellence Program 2000-2005), the University of Helsinki, Biocentrum Helsinki, Sigrid Juselius Foundation, the Finnish Cancer Foundation and HUCH EVO grants. We thank Ms. Virpi Päivinen and Ms. Maija Hälikkä for excellent technical assistance.

PY - 2002/9/11

Y1 - 2002/9/11

N2 - Transforming growth factor-β (TGF-β) signaling relies on Smad-signaling pathway controlled in part by the proteasome. Here we demonstrate that inhibition of the proteasome function in mink epithelial cells accumulates both positive and negative modulators of TGF-β signaling, phospho-Smad2 and SnoN. Inhibition of the proteasome led to abrogation of TGF-β target gene regulation in a gene-specific manner. While regulation of p15Ink4b and myc by TGF-β are lost, PAI-1 induction, previously shown to occur in a Smad3-dependent manner, was not affected by treatment of the cells with the proteasomal inhibitor MG132. The results suggest that proteasomal activity is required for TGF-β signaling in a gene-specific manner.

AB - Transforming growth factor-β (TGF-β) signaling relies on Smad-signaling pathway controlled in part by the proteasome. Here we demonstrate that inhibition of the proteasome function in mink epithelial cells accumulates both positive and negative modulators of TGF-β signaling, phospho-Smad2 and SnoN. Inhibition of the proteasome led to abrogation of TGF-β target gene regulation in a gene-specific manner. While regulation of p15Ink4b and myc by TGF-β are lost, PAI-1 induction, previously shown to occur in a Smad3-dependent manner, was not affected by treatment of the cells with the proteasomal inhibitor MG132. The results suggest that proteasomal activity is required for TGF-β signaling in a gene-specific manner.

KW - Proteasome

KW - Signaling

KW - Smad

KW - SnoN

KW - Transforming growth factor-β

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SN - 0014-5793

VL - 527

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EP - 62

JO - FEBS Letters

JF - FEBS Letters

IS - 1-3

ER -

Proteasomal activity modulates TGF-β signaling in a gene-specific manner

Abstract

Keywords

ASJC Scopus subject areas

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