Transcription factor AP-4 contains multiple dimerization domains that regulate dimer specificity.
10.1101/gad.4.10.1741
Crossref journal-article
Cold Spring Harbor Laboratory
Genes & Development (246)
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.

Bibliography

Hu, Y. F., Lüscher, B., Admon, A., Mermod, N., & Tjian, R. (1990). Transcription factor AP-4 contains multiple dimerization domains that regulate dimer specificity. Genes & Development, 4(10), 1741–1752.

Authors 5
  1. Y F Hu (first)
  2. B Lüscher (additional)
  3. A Admon (additional)
  4. N Mermod (additional)
  5. R Tjian (additional)
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Dates
Type When
Created 18 years, 2 months ago (June 5, 2007, 5:15 p.m.)
Deposited 3 years, 9 months ago (Nov. 13, 2021, 11:15 p.m.)
Indexed 2 months, 2 weeks ago (June 15, 2025, 2:41 a.m.)
Issued 34 years, 10 months ago (Oct. 1, 1990)
Published 34 years, 10 months ago (Oct. 1, 1990)
Published Online 34 years, 10 months ago (Oct. 1, 1990)
Published Print 34 years, 10 months ago (Oct. 1, 1990)
Funders 0

None

@article{Hu_1990, title={Transcription factor AP-4 contains multiple dimerization domains that regulate dimer specificity.}, volume={4}, ISSN={1549-5477}, url={http://dx.doi.org/10.1101/gad.4.10.1741}, DOI={10.1101/gad.4.10.1741}, number={10}, journal={Genes & Development}, publisher={Cold Spring Harbor Laboratory}, author={Hu, Y F and Lüscher, B and Admon, A and Mermod, N and Tjian, R}, year={1990}, month=oct, pages={1741–1752} }