Post-translational modifications of HOX proteins, an underestimated issue

Abstract

Post-translational modifications (PTMs) are important determinants which contribute to modulating the turn-over, intracellular localisation, molecular interactions and activity of most eukaryotic proteins. Such modifications and their consequences have been extensively examined for some proteins or classes of proteins. This is not the case for the HOX transcription factors which are crucial regulators of animal development. In this review, we provide a survey of the literature and data repositories pertaining to HOX-associated PTMs. This highlights that HOX proteins are also likely widely post-translationally modified, and defines HOX PTMs as an under-valued facet of their biology.

Multi-level and lineage-specific interactomes of the Hox transcription factor Ubx contribute to its functional specificity

“…Thus, it is tempting to speculate that the different interactomes assembled by Ubx in the mesodermal and neural lineages are also dependent on specific post-translational modifications, which are cell type-and stage-specifically written on intrinsically disordered domains of Ubx. Consistently, it is now more and more realized that Hox TFs are heavily modified at the post-translational level 67,68 . In future, it will be crucial to characterize Ubx-Tin and Ubx-Grh complexes on the structuralfunctional level and to study cell type-specific post-translational modifications of Ubx in vivo to resolve the specificity problem intrinsic to Hox TFs.…”

Posttranslational Modifications in Conserved Transcription Factors: A Survey of the TALE-Homeodomain Superclass in Human and Mouse

“…Monomeric PBX proteins or PBX-MEINOX dimers form cell type-specific transcriptional regulatory units with other TFs, including HD transcription factor like HOXproteins, basic helix-loop-helix (bHLH), nuclear receptors, Smad2,3,4 intracellular signaling proteins of the TGF-β pathway, as well as chromatin modifying enzymes (Peltenburg and Murre, 1996;Wang et al, 2001;Subramaniam et al, 2003;Bailey et al, 2004;Choe et al, 2009Choe et al, , 2014Merabet and Galliot, 2015). In fact, PBC-class proteins are essential cofactors of HOX-proteins, which themselves are subject to multiple forms of PTM (Draime et al, 2018). Pbx1, Pbx2, and Pbx3 are extensively co-expressed and can partly compensate for each other in domains of co-expression (Selleri et al, 2001(Selleri et al, , 2004Rhee et al, 2004;Capellini et al, 2006).…”

“…The ability of a TF to interact with DNA or with other proteins depends on the biochemical properties of the amino acids involved in binding, which in turn can be profoundly altered by the attachment of additional chemical moieties in a process known as posttranslational modification (PTM). Consequently, the type of binding partners a TF assembles with, the sequence motif recognized by the complex, and the strength of interaction with this motif are sensitive to PTMs (Filtz et al, 2014;Draime et al, 2018). These are important features for any TF, because the composition of transcriptional multiprotein complexes determines the cellular and physiological context in which the TF acts, while recognition of motif variations can lead to high-or low affinity DNA binding, which in turn may result in dynamic gene expression levels (Crocker et al, 2016).…”

Post-translational modifications of Drosophila melanogaster HOX protein, Sex combs reduced

“…Interactions with the cofactor Extradenticle (EXD) is one mechanism proposed to mediate the functional specificity of HOX proteins. In addition to HOX cofactor protein interactions, PTMs are also proposed to have a role in the regulation of functional specificity [4][5][6]. Here the PTMs of a HOX protein, Sex combs reduced (SCR) are mapped as a first step towards understanding this regulation of HOX protein activity.…”