The human forkhead protein FREAC-2 contains two functionally redundant activation domains and interacts with TBP and TFIIB.
Forkhead-related activator 2 (FREAC-2) is a human transcription factor expressed in lung and placenta that binds to cis-elements in several lung-specific genes. We have identified the parts of FREAC-2 responsible for trans-activation and found two functionally redundant activation domains on the C-terminal side of the DNA binding forkhead domain. Activation domain 1 consists of the most C-terminal 23 amino acids of FREAC-2 and contains a sequence motif conserved in an activation domain of another forkhead protein, FREAC-1. Activation domain 2 is built up by three synergistic subdomains in the central part of the FREAC-2 protein. FREAC-2 was shown to interact in vitro with TBP and TFIIB. The target site for FREAC-2 on TBP was localized to the N-terminal repeat in the core domain of TBP. TFIIB binds FREAC-2 close to the cleft between its two globular domains. The part of FREAC-2 that binds TBP was mapped to 21 amino acids in the C-terminal end of the forkhead domain. This sequence is well conserved among forkhead proteins, raising the possibility that interaction with TBP may be a general characteristic of this family of transcription factors. Overexpression of TFIIB potentiates activation by FREAC-2 in a manner dependent on the FREAC-2 activation domains. Nuclear localization of FREAC-2 was found to depend on sequences from both ends of the forkhead domain.
Department of Molecular Biology, Göteborg University, Medicinaregatan 9C, Box 462, S-405 30 Göteborg, Sweden.
M
M
Hellqvist
M
M
Mahlapuu
A
A
Blixt
S
S
Enerbäck
P
P
Carlsson
D000595:Amino Acid Sequence; D001665:Binding Sites; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D051858:Forkhead Transcription Factors; D017930:Genes, Reporter; D006801:Humans; D008957:Models, Genetic; D008969:Molecular Sequence Data; D016296:Mutagenesis; D019913:Nuclear Localization Signals; D011485:Protein Binding; D011994:Recombinant Proteins / Q000378:metabolism; D015398:Signal Transduction; D035181:TATA-Box Binding Protein; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D035581:Transcription Factor TFIIB; D014157:Transcription Factors / Q000378:metabolism*; D015533:Transcriptional Activation
D004268:DNA-Binding Proteins; C486413:FOXF2 protein, human; D051858:Forkhead Transcription Factors; C114562:LUN protein, vertebrate; D019913:Nuclear Localization Signals; D011994:Recombinant Proteins; D035181:TATA-Box Binding Protein; D015534:Trans-Activators; D035581:Transcription Factor TFIIB; D014157:Transcription Factors