Kinase Regulation of HOX Transcription Factors.

Monika Primon,Keith D Hunter,Richard Morgan,Hardev S Pandha

doi:10.3390/cancers11040508

Monika Primon, Keith D Hunter + Show 2 more

Open Access

https://doi.org/10.3390/cancers11040508

Copy DOI

Abstract

The HOX genes are a group of homeodomain-containing transcription factors that play important regulatory roles in early development, including the establishment of cell and tissue identity. HOX expression is generally reduced in adult cells but is frequently re-established as an early event in tumour formation and supports an oncogenic phenotype. HOX transcription factors are also involved in cell cycle regulation and DNA repair, along with normal adult physiological process including stem cell renewal. There have been extensive studies on the mechanism by which HOX proteins regulate transcription, with particular emphasis on their interaction with cofactors such as Pre-B-cell Leukaemia Homeobox (PBX) and Myeloid Ecotropic Viral Integration Site 1 (MEIS). However, significantly less is known of how the activity of HOX proteins is regulated. There is growing evidence that phosphorylation may play an important role in this context, and in this review, we draw together a number of important studies published over the last 20 years, and discuss the relevance of phosphorylation in the regulation and function of HOX proteins in development, evolution, cell cycle regulation, and cancer.

Highlights

The HOX genes encode a family of homeodomain-containing transcription factors that play important roles in the early embryo, including the establishment of cell and tissue identity, and the regulation of cell proliferation, differentiation, and survival [1]
The highly conserved homeodomain of HOX proteins mediates their binding to DNA, the strength and specificity of this interaction is greatly increased by the binding of co-factors such as Pre-B-cell Leukaemia Homeobox (PBX), which forms heterodimers with HOX proteins in groups
Givenstrategy the profound homeotic activity of HOX genes and their ability to influence processes in is to inhibit the interaction between HOX and PBX, which is mediated by a conserved the adult, including repair and cell cycle regulation, is relatively little known of how HOX

Summary

Introduction

The HOX genes encode a family of homeodomain-containing transcription factors that play important roles in the early embryo, including the establishment of cell and tissue identity, and the regulation of cell proliferation, differentiation, and survival [1]. Givenstrategy the profound homeotic activity of HOX genes and their ability to influence processes in is to inhibit the interaction between HOX and PBX, which is mediated by a conserved the adult, including repair and cell cycle regulation, is relatively little known of how HOX hexapeptideDNA sequence in HOX. This interaction can there be inhibited using HXR9, a small peptide mimicregulated.

Kinase

Casein

Potential

Kinase Regulation of HOX Proteins during the Cell Cycle

Kinase Regulation of HOX Proteins in Disease

Conclusions