Transcription factor AP-4 contains multiple dimerization domains that regulate dimer specificity.

Details

Serval ID
serval:BIB_52019A23F870
Type
Article: article from journal or magazin.
Collection
Publications
Title
Transcription factor AP-4 contains multiple dimerization domains that regulate dimer specificity.
Journal
Genes and Development
Author(s)
Hu Y.F., Lüscher B., Admon A., Mermod N., Tjian R.
ISSN
0890-9369[print], 0890-9369[linking]
Publication state
Published
Issued date
10/1990
Volume
4
Number
10
Pages
1741-1752
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, P.H.S.
Publication Status: ppublish
Abstract
Enhancer binding protein AP-4 is a transcription factor that activates both viral and cellular genes by binding to the symmetrical DNA sequence, CAGCTG. Here, we report the molecular cloning and characterization of human AP-4 cDNAs. The deduced amino acid sequence reveals that AP-4 is a helix-loop-helix (HLH) protein. Like other members of this family, the AP-4 HLH motif and the adjacent basic domain are necessary and sufficient to confer site-specific DNA binding. However, unlike other HLH proteins, AP-4 also contains two additional protein dimerization motifs consisting of leucine repeat elements LR1 and LR2. The analysis of various deletion and point mutants for their ability to dimerize in the presence or absence of DNA reveals several unusual features. Although the HLH basic region is sufficient for DNA recognition and binding, dimer formation between different truncated versions of AP-4 in solution requires an intact LR1 or LR2 domain. AP-4 is unable to form heterodimers with other helix-loop-helix family members such as the immunoglobulin enhancer binding factor, E12. In contrast, an AP-4 derivative, delta C222, which lacks LR1 and LR2 but retains an intact HLH, can form heterodimers with E12. Moreover, AP-4 molecules containing LR2 or LR1 are unable to form mixed dimers with carboxy-terminally truncated AP-4 molecules such as delta C222, but retain the ability to form complexes with longer versions of AP-4 that contain LR1 and/or LR2. Our findings strongly suggest that AP-4 contains multiple protein-protein interfaces that function to promote homodimer formation and restrict heterocomplexes. These findings provide a mechanism by which different members of the helix-loop-helix family of transcription factors can form functional dimers in a specific fashion with their appropriate partners to control transcriptional networks during cellular differentiation.
Keywords
Amino Acid Sequence, Base Sequence, Biopolymers, Cross-Linking Reagents, DNA/isolation &amp, purification, DNA-Binding Proteins/chemistry, DNA-Binding Proteins/genetics, Genetic Vectors, Glutaral, Hela Cells, Humans, Leucine/genetics, Molecular Sequence Data, Protein Biosynthesis/genetics, Sensitivity and Specificity, Transcription Factors/chemistry, Transcription Factors/genetics, Transcription, Genetic/genetics, Vaccinia virus/genetics
Pubmed
Web of science
Open Access
Yes
Create date
24/01/2008 11:41
Last modification date
08/05/2019 18:36
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