HOX Protein Activity Regulation by Cellular Localization

Laure Bridoux,Françoise Gofflot,René Rezsohazy

doi:10.3390/jdb9040056

Laure Bridoux, Françoise Gofflot + Show 1 more

Open Access

https://doi.org/10.3390/jdb9040056

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Abstract

While the functions of HOX genes have been and remain extensively studied in distinct model organisms from flies to mice, the molecular biology of HOX proteins remains poorly documented. In particular, the mechanisms involved in regulating the activity of HOX proteins have been poorly investigated. Nonetheless, based on data available from other well-characterized transcription factors, it can be assumed that HOX protein activity must be finely tuned in a cell-type-specific manner and in response to defined environmental cues. Indeed, records in protein–protein interaction databases or entries in post-translational modification registries clearly support that HOX proteins are the targets of multiple layers of regulation at the protein level. In this context, we review here what has been reported and what can be inferred about how the activities of HOX proteins are regulated by their intracellular distribution.

Highlights

HOX proteins define a family of transcription factors (TFs) initially identified to be crucial actors in controlling the fate of embryonic territories during animal development [1]
This clustering of Hox genes has been maintained in most bilaterian phyla, some clades underwent a dismantling of their Hox clusters, as observed in the nematode Caenorhabditis elegans or in ascidians [6,7]
HOX proteins were shown to interact with TFs and, significantly, with proteins that are not known to be related to gene regulation

Summary

Introduction

HOX proteins define a family of transcription factors (TFs) initially identified to be crucial actors in controlling the fate of embryonic territories during animal development [1]. In addition to their critical involvement in patterning the animal body plan, studies about the functions of HOX proteins revealed that they participate in organ development, cell differentiation or cell stemness regulation They maintain activities in adulthood as exemplified in hematopoiesis, neuronal circuit establishment and refinement, or tissue regeneration [10–14]. HOX proteins were shown to interact with TFs and, significantly, with proteins that are not known to be related to gene regulation This includes proteins linked to distinct cellular processes such as cell-trafficking, post-translational modification (PTM) of proteins, signal transduction, DNA repair, cell cycling, among many others [23–26]. While recent reviews have focused on the PTMs of HOX proteins, here, we will survey fragmentary data about HOX protein intracellular redistribution, its control and its consequences

HOX Protein Localization

NLS, Predictions and Validations

Leaving the Nucleus

Leaving the Nucleus to Leave Cells?

Interactions with Karyopherins and Proteins Associated with Cytoplasmic Organelles