Ubiquitin‐proteasome‐dependent degradation of TBP‐like protein is prevented by direct binding of TFIIA

• Published in: Genes to cells : devoted to molecular & cellular mechanisms 2016-11, Vol.21 (11), p.1223-1232
• Main Authors: Isogai, Momoko, Suzuki, Hidefumi, Maeda, Ryo, Tamura, Taka‐aki
• Format: Article
• Language: English
• Subjects: Animals; Binding, Competitive; Gene Expression Regulation; HCT116 Cells; HeLa Cells; Humans; Mice; Proteasome Endopeptidase Complex - metabolism; Protein Binding; Protein Stability; Proteolysis; TATA Box Binding Protein-Like Proteins - metabolism; TATA-Box Binding Protein - metabolism; Transcription Factor TFIIA - metabolism; Ubiquitin - metabolism
• ISSN: 1356-9597; 1365-2443
• DOI: 10.1111/gtc.12441

Although the majority of gene expression is driven by TATA‐binding protein (TBP)‐based transcription machinery, it has been reported that TBP‐related factors (TRFs) are also involved in the regulation of gene expression. TBP‐like protein (TLP), which is one of the TRFs and exhibits the highest affinity to TFIIA among known proteins, has recently been showed to have significant roles in gene regulation. However, how the level of TLP is maintained in vivo has remained unknown. In this study, we explored the mechanism by which TLP protein is turned over in vivo and the factor that maintains the amount of TLP. We showed that TLP is rapidly degraded by the ubiquitin‐proteasome system and that tight interaction with TFIIA results in protection of TLP from ubiquitin‐proteasome‐dependent degradation. The half‐life of TLP was shown to be less than a few hours, and the proteasome inhibitor MG132 specifically suppressed TLP degradation. Moreover, knockdown and over‐expression experiments showed that TFIIA is engaged in stabilization of TLPin vivo. Thus, we showed a novel characteristic of TLP, that is, interaction with TFIIA is essential to suppress proteasome‐dependent turnover of TLP, providing a further insight into TLP‐governed gene regulation. TBP‐family protein TLP is degraded by ubiquitin‐proteasome pathway. We showed that the degradation of TLP is prevented by TFIIA. Our data suggest that the TFIIA‐induced TLP stabilization is required for transcription regulation.