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1.
Genes Cells ; 21(11): 1223-1232, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-27696626

RESUMO

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.


Assuntos
Complexo de Endopeptidases do Proteassoma/metabolismo , Proteínas Semelhantes à Proteína de Ligação a TATA-Box/metabolismo , Fator de Transcrição TFIIA/metabolismo , Ubiquitina/metabolismo , Animais , Ligação Competitiva , Regulação da Expressão Gênica , Células HCT116 , Células HeLa , Humanos , Camundongos , Ligação Proteica , Estabilidade Proteica , Proteólise , Proteína de Ligação a TATA-Box/metabolismo
2.
Nucleic Acids Res ; 43(13): 6285-98, 2015 Jul 27.
Artigo em Inglês | MEDLINE | ID: mdl-26038314

RESUMO

TBP-TFIIA interaction is involved in the potentiation of TATA box-driven promoters. TFIIA activates transcription through stabilization of TATA box-bound TBP. The precursor of TFIIA is subjected to Taspase1-directed processing to generate α and ß subunits. Although this processing has been assumed to be required for the promoter activation function of TFIIA, little is known about how the processing is regulated. In this study, we found that TBP-like protein (TLP), which has the highest affinity to TFIIA among known proteins, affects Taspase1-driven processing of TFIIA. TLP interfered with TFIIA processing in vivo and in vitro, and direct binding of TLP to TFIIA was essential for inhibition of the processing. We also showed that TATA box promoters are specifically potentiated by processed TFIIA. Processed TFIIA, but not unprocessed TFIIA, associated with the TATA box. In a TLP-knocked-down condition, not only the amounts of TATA box-bound TFIIA but also those of chromatin-bound TBP were significantly increased, resulting in the stimulation of TATA box-mediated gene expression. Consequently, we suggest that TLP works as a negative regulator of the TFIIA processing and represses TFIIA-governed and TATA-dependent gene expression through preventing TFIIA maturation.


Assuntos
Endopeptidases/metabolismo , Proteínas Repressoras/metabolismo , Proteínas Semelhantes à Proteína de Ligação a TATA-Box/metabolismo , TATA Box , Fator de Transcrição TFIIA/metabolismo , Ativação Transcricional , Linhagem Celular , Cromatina/metabolismo , Células HeLa , Humanos , Proteína de Ligação a TATA-Box/metabolismo
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