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Kajino, T. et al.

TAK1 MAPK Kinase Kinase Mediates Transforming Growth Factor-beta Signaling by Targeting SnoN Oncoprotein for Degradation.

Transforming growth factor-beta (TGF-beta) regulates a variety of physiologic processes through essential intracellular mediators Smads. The SnoN oncoprotein is an inhibitor of TGF-beta signaling. SnoN recruits transcriptional repressor complex to block Smad-dependent transcriptional activation of TGF-beta-responsive genes. Following TGF-beta stimulation, SnoN is rapidly degraded, thereby allowing the activation of TGF-beta target genes. Here, we report the role of TAK1 as a SnoN protein kinase. TAK1 interacted with and phosphorylated SnoN, and this phosphorylation regulated the stability of SnoN. Inactivation of TAK1 prevented TGF-beta- induced SnoN degradation and impaired induction of the TGF-beta-responsive genes. These data suggest that TAK1 modulates TGF-beta-dependent cellular responses by targeting SnoN for degradation.[1]

References

TAK1 MAPK Kinase Kinase Mediates Transforming Growth Factor-beta Signaling by Targeting SnoN Oncoprotein for Degradation. Kajino, T., Omori, E., Ishii, S., Matsumoto, K., Ninomiya-Tsuji, J. J. Biol. Chem. (2007) [Pubmed]

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