HOPX: The Unusual Homeodomain-Containing Protein

Abstract

The homeodomain-only protein homeobox (HOPX) is the smallest known member of the homeodomain-containing protein family, atypically unable to bind DNA. HOPX is widely expressed in diverse tissues, where it is critically involved in the regulation of proliferation and differentiation. In human skin, HOPX controls epidermal formation through the regulation of late differentiation markers, and HOPX expression correlates with the level of differentiation in cutaneous pathologies. In mouse skin, Hopx was additionally identified as a lineage tracing marker of quiescent hair follicle stem cells. This review discusses current knowledge of HOPX structure and function in normal and pathological conditions.

HOPX functions as a tumour suppressor in head and neck cancer

“…Interestingly, this methylation correlated with a worse overall survival in HPV negative HNSCCs, which supports previous studies showing an association between HOPX-β promoter hypermethylation and patient prognosis821. It is noteworthy that we identified the five recently reported HOPX isoforms (that code for protein isoforms a, b and c)9 plus two apparently non-coding transcripts in the TCGA HNSCC RNASeq data. Clearly, the biological functions of HOPX in human tissues are more complex than previously thought and studies to elucidate the function of the HOPX isoforms, together with the identification of isoform- and tissue-specific binding partners are warranted.…”

“…Collectively, our results demonstrate that HOPX regulates the transcription of genes associated with epithelial homeostasis. Whilst it will be important to confirm these findings in normal keratinocytes following knockdown of endogenous HOPX, our data are entirely consistent with observations that HOPX regulates the balance between proliferation and differentiation in a number of cell types and controls late terminal differentiation in keratinocytes922.…”

“…There are three reported splice variants of the HOPX gene (HOPX-α, HOPX-β and HOPX-γ) that code for the same protein8. However, recent analysis of NCBI reference sequences indicates that there are five transcripts that encode three different proteins9, although the expression of these transcripts in different tissues has not yet been examined. The HOPX-β promoter contains CpG islands that are methylated in various cancers leading to down-regulation of HOPX expression, strongly suggesting that HOPX functions as a tumour suppressor81011.…”

A single-cell reference map for human blood and tissue T cell activation reveals functional states in health and disease

“…An Interferon (IFN) Response module enriched among activated CD4 + T cells included multiple gene families associated with canonical IFN responses [41][42][43] (IFIT3, IFIT2, STAT1, MX1, IRF7, and JAK2). In contrast, CD8 + T cell-enriched modules included a Cytotoxic module containing genes associated with cytotoxicity (GNLY, GZMK) and transcription factors associated with effector/memory differentiation (ZEB2, EOMES, ZNF683) [43][44][45] , and a Cytokine module with genes encoding chemokines and cytokines (CCL3, CCL4, CCL20, IFNG, IL10, 1 1 TNF), inhibitory molecules (LAG3, CD226 (TIGIT), HAVCR2 (TIM3)), and the widely expressed homeobox protein HOPX 46 . These results indicate a limited spectrum of functional states for human T cells across blood and tissue sites.…”

The role of miRNA regulation in fetal cardiomyocytes, cardiac maturation and the risk of heart disease in adults

“…miR‐590‐3p and miR‐199a‐3p share several of the same targets including Homer1 , which encodes a protein that modulates Ca 2+ signalling in the heart through interaction with the Ca 2+ release channel ryanodine receptor (RyR) (Fill & Copello, ). In addition, both miRNAs also target the mRNA of HOP homeobox ( HOPX ), which encodes a homeodomain protein that inhibits cardiomyocyte proliferation (Mariotto et al . 2016).…”