The adenovirus E1A repression domain disrupts the interaction between the TATA binding protein and the TATA box in a manner reversible by TFIIB.

AUTOR(ES)

Song, C Z

RESUMO

The human adenovirus E1A 243 amino acid oncoprotein possesses a transcription repression function that appears to be linked with its ability to induce cell cycle progression and to inhibit cell differentiation. The molecular mechanism of E1A repression has been poorly understood. Recently, we reported that the TATA binding protein (TBP) is a cellular target of E1A repression. Here we demonstrate that the interaction between TBP and the E1A repression domain is direct and specific. The TBP binding domain within E1A 243R maps to E1A N-terminal residues approximately 1 to 35 and is distinct from the TBP binding domain within conserved region 3 unique to the E1A 289R transactivator. An E1A protein fragment consisting of only the E1A N-terminal 80 amino acids (E1A 1-80) and containing the E1A repression function was found to block the interaction between TBP and the TATA box element as shown by gel mobility and DNase protection analysis. Interestingly, a preformed TBP-TATA box promoter complex can be dissociated by E1A 1-80. Further, TFIIB can prevent E1A disruption of TBP-TATA box interaction. TFIIB, like TBP, can overcome E1A repression of transcription in vitro. The ability of the E1A repression domain to block TBP interaction with the TATA box and the ability of TFIIB to reverse E1A disruption of the TBP-TATA box complex implies a mechanism for E1A repression distinct from those of known cellular repressors that target TBP.

Documentos Relacionados

• Direct interaction between adenovirus E1A protein and the TATA box binding transcription factor IID.
• The zinc finger region of the adenovirus E1A transactivating domain complexes with the TATA box binding protein.
• Two domains of p53 interact with the TATA-binding protein, and the adenovirus 13S E1A protein disrupts the association, relieving p53-mediated transcriptional repression.
• Repression of activator-mediated transcription by herpes simplex virus ICP4 via a mechanism involving interactions with the basal transcription factors TATA-binding protein and TFIIB.
• Interaction between the N-terminal domain of the 230-kDa subunit and the TATA box-binding subunit of TFIID negatively regulates TATA-box binding.