Fasciculation and elongation zeta‐1 protein (FEZ1) interacts with the retinoic acid receptor and participates in transcriptional regulation of the Hoxb4 gene

Abstract

Fasciculation and elongation zeta‐1 (FEZ1) protein is involved in axon outgrowth and is highly expressed in the brain. It has multiple interaction partners, with functions varying from the regulation of neuronal development and intracellular transport mechanisms to transcription regulation. One of its interactors is retinoic acid receptor (RAR), which is activated by retinoic acid and controls many target genes and physiological process. Based on previous evidence suggesting a possible nuclear role for FEZ1, we wanted to deepen our understanding of this function by addressing the FEZ1–RAR interaction. We performed in vitro binding experiments and assessed the interface of interaction between both proteins. We found that FEZ1–RAR interacted with a similar magnitude as RAR to its responsive element DR5 and that the interaction occurred in the coiled‐coil region of FEZ1 and in the ligand‐binding domain of RAR. Furthermore, cellular experiments were performed in order to confirm the interaction and screen for induced target genes from an 86‐gene panel. The analysis of gene expression showed that only in the presence of retinoic acid did FEZ1 induce hoxb4 gene expression. This finding is consistent with data from the literature showing the hoxb4 gene functionally involved in development and acute myeloid leukemia, as is FEZ1.

NEDD9 overexpression: Prognostic and guidance value in acute myeloid leukaemia

“…The top 10 upregulated genes such as FEZ1 and PDK4 are reported with proto-leukaemia effects. 27,28 Furthermore, the Gene Ontology analysis revealed that these genes involved in biologic processes, including multicellular organismal process, cell communication and signalling (Figure 5C). groups (Figure 5D and Table S1).…”

The Actin Binding Protein Plastin-3 Is Involved in the Pathogenesis of Acute Myeloid Leukemia

“…Overexpression of FEZ1 in HEK293 and HeLa cells resulted in multi-lobulated nuclei as often observed in human leukemia cells [29]. Furthermore, it was shown that FEZ1 interacts with the retinoic acid receptor (RAR) thereby regulating the transcription of the HOXB4 gene [30]. HOXB4 has been implicated as a tumor-related gene in many cancer entities, including leukemia where it is also related to poor prognosis and chemoresistance [31,32,33].…”

Fasciculation and elongation zeta proteins 1 and 2: From structural flexibility to functional diversity

“…In this context, it was recently reported that Sox2 gene was induced when FEZ1 was over-expressed in U87 cells and this was confirmed when FEZ1 was depleted and there was no Sox2 activation, supporting the hypothesis that the presence of FEZ1 could be part of a regulatory complex responsible for Sox2 activation. Moreover, the authors also reported a dramatic induction of Hoxb4 gene in the context of FEZ1 over-expression and the interaction with the retinoic acid receptor (RAR), in the presence of the ligand retinoic acid[61]. Hoxb4 is known to be related to development[62] and experiments showed Fez1 expression by in situ hybridization in chicken embryos during neurulation and somitogenesis (Kobarg et al, non-published observation).…”