Polyubiquitination of Transforming Growth Factor β(TGFβ)-associated Kinase 1 Mediates Nuclear Factor-κB Activation in Response to Different Inflammatory Stimuli

Hamidi, A.; von Bulow, V.; Hamidi, R.; Winssinger, Nicolas; Barluenga, S.; Heldin, C.-H.; Landstrom, M.

doi:10.1074/jbc.M111.285122

Scientific article

English

Polyubiquitination of Transforming Growth Factor β(TGFβ)-associated Kinase 1 Mediates Nuclear Factor-κB Activation in Response to Different Inflammatory Stimuli

Contributors

Hamidi, A.; von Bulow, V.; Hamidi, R.; Winssinger, Nicolas

; Barluenga, S.; Heldin, C.-H.; Landstrom, M.

Published in

The Journal of biological chemistry, vol. 287, no. 1, p. 123-133

Publication date

2012

Abstract

The transcription factor nuclear factor κB (NF-κB) plays a central role in regulating inflammation in response to several external signals. The TGFβ-associated kinase 1 (TAK1) is an upstream regulator of NF-κB signaling. In TGFβ-stimulated cells, TAK1 undergoes Lys-63-linked polyubiquitination at Lys-34 by TNF receptor-associated factor 6 and is thereby activated. The aim of this study was to investigate whether TAK1 polyubiquitination at Lys-34 is also essential for NF-κB activation via TNF receptor, IL-1 receptor and toll-like receptor 4. We observed that TAK1 polyubiquitination occurred at Lys-34 and required the E3 ubiquitin ligase TNF receptor-associated factor 6 after stimulation of cells with IL-1β. Polyubiquitination of TAK1 also occurred at Lys-34 in cells stimulated by TNF-α and LPS, which activates TLR4, as well as in HepG2 and prostate cancer cells stimulated with TGFβ, which in all cases resulted in NF-κB activation. Expression of a K34R-mutant TAK1 led to a reduced NF-κB activation, IL-6 promoter activity, and proinflammatory cytokine secretion by TNF-α-stimulated PC-3U cells. Similar results were obtained in the mouse macrophage cell line RAW264.7 after LPS treatment. In conclusion, polyubiquitination of TAK1 is correlated with activation of TAK1 and is essential for activation of NF-κB signaling downstream of several receptors.

UNIGE affiliation entities

Not a UNIGE publication

Citation (ISO format)

HAMIDI, A. et al. Polyubiquitination of Transforming Growth Factor β(TGFβ)-associated Kinase 1 Mediates Nuclear Factor-κB Activation in Response to Different Inflammatory Stimuli. In: The Journal of biological chemistry, 2012, vol. 287, n° 1, p. 123–133. doi: 10.1074/jbc.M111.285122

Article (Published version)

Identifiers

PID : unige:24673
DOI : 10.1074/jbc.M111.285122

Journal ISSN

0021-9258

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Creation

12/12/2012 10:35:00

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12/12/2012 10:35:00

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13/10/2025 23:52:57

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14/03/2023 17:47:34

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01/07/2026 06:09:34

Polyubiquitination of Transforming Growth Factor β(TGFβ)-associated Kinase 1 Mediates Nuclear Factor-κB Activation in Response to Different Inflammatory Stimuli

Contributors

Published in

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Abstract

UNIGE affiliation entities

Citation (ISO format)

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First validation

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Status update

Last indexation