TRIM11 binds to and destabilizes a key component of the activator-mediated cofactor complex (ARC105) through the ubiquitin-proteasome system.
TRIM11 is a member of the tripartite-motif-containing protein family and is known to destabilize humanin, an inhibitor of Alzheimer-like neuronal insults. In this study, we demonstrate that TRIM11 interacts with activator-recruited cofactor 105-kDa component (ARC105) that mediates chromatin-directed transcription activation and is a key regulatory factor for transforming growth factor beta (TGFbeta) signaling. Co-expression of TRIM11 increased ARC105 degradation but a proteasome inhibitor suppressed this. Co-expression of TRIM11 and ARC105 also increased ubiquitination of ARC105. In addition, TRIM11 suppressed ARC105-mediated transcriptional activation induced with TGFbeta in a reporter assay. These results suggest that TRIM11, with the ubiquitin-proteasome pathway, regulates ARC105 function in TGFbeta signaling.
Ishikawa
Hideaki
H
Department of Bioengineering, Applied Life Science, United Graduate School of Agriculture, Tokyo University of Agriculture and Technology, 3-5-8 Saiwai-cho, Fuchu-shi, Tokyo 183-8509, Japan.
Tachikawa
Hiroyuki
H
Miura
Yutaka
Y
Takahashi
Nobuhiro
N
D000818:Animals; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D017930:Genes, Reporter; D006801:Humans; D056892:Mediator Complex; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D015533:Transcriptional Activation / Q000502:physiology; D016212:Transforming Growth Factor beta / Q000378:metabolism*; D000070584:Tripartite Motif Proteins; D025801:Ubiquitin / Q000378:metabolism*; D044767:Ubiquitin-Protein Ligases
D002352:Carrier Proteins; C416944:MED15 protein, human; D056892:Mediator Complex; D011993:Recombinant Fusion Proteins; D014157:Transcription Factors; D016212:Transforming Growth Factor beta; D000070584:Tripartite Motif Proteins; D025801:Ubiquitin; C510874:TRIM11 protein, human; D044767:Ubiquitin-Protein Ligases; D046988:Proteasome Endopeptidase Complex