Elsevier

Biochemical Pharmacology

Volume 58, Issue 12, 15 December 1999, Pages 1851-1857
Biochemical Pharmacology

Commentaries
The homeodomain-containing proteins: An update on their interacting partners

https://doi.org/10.1016/S0006-2952(99)00234-8Get rights and content

Abstract

Homeodomain-containing proteins are transcription regulators controlling the coordinated expression of genes involved in development, differentiation, and cellular transformation. They share a highly conserved 60-amino-acid region (the “homeodomain”), which allows them to bind DNA and modulate the expression of multiple target genes, whose identities remain largely unknown. Although each HOX gene product exhibits in vivo specificity, they harbor very similar DNA-binding affinities in vitro, suggesting that other mechanisms such as protein–protein interactions are critical to modulate their function. In this commentary, we describe the proteins that can interact with the HOX gene products, including newly identified partners such as CREB binding protein and the NF-κB/IκB-α proteins. We also outline the molecular programs that are regulated by the transcriptional complexes involving the HOX gene products and where new pharmacological tools could find interesting targets.

Section snippets

In vitro and in vivo specificities of the Hox gene products: Role of the cofactors

DNA–protein interactions clearly contribute to the in vivo specificity of each HOX protein 18, 19. The identification of the functional domains of HOX gene products appears to depend on the target DNA sequence but also on the physiological context in which the HOX proteins interact with the DNA [20], thus suggesting that interactions with other proteins, defined as “cofactors,” are required to regulate their function.

In the search for Hox interacting partners, the first candidates to be

Conclusions

Significant progress has been made recently regarding the molecular characterization of the transcriptional complexes involving HOX gene products. The aim of this commentary was to demonstrate tentatively that elucidation of genetic programs regulated by HOX genes can be achieved through identification of HOX interacting partners. Although it is likely that most of the actors still have to be defined, it is clear that further investigations regarding the way the known HOX partners interact with

Acknowledgements

The authors are grateful to Carine van Lint for helpful discussions and to Ulrich Siebenlist for his support. Alain Chariot is a Research Assistant at the University of Liege and is supported by postdoctoral grants from the NATO and the Fulbright Commission. Vincent Bours and Marie-Paule Merville are Research Associates of the National Fund for Scientific Research (“FNRS,” Belgium).

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