Table 1 Summary of HOXA9 binding partners and its mechanisms
From: Role of HOXA9 in solid tumors: mechanistic insights and therapeutic potential
Binding partners | Mechanisms | PMID | References |
|---|---|---|---|
PBX3 | PBX3 showed a synergistic effect with HOXA9 in inducing leukemia, and small peptide HXR9 disrupted the PBX3/HOXA9 interaction leading to the inhibition of cell proliferation and promotes apoptosis in AML cells | [59] | |
MEIS1 | HOXA9 physically interacted with MEIS1 which is also a cofactor of HOXA9, SCUBE1 is confirmed as a novel target of HOXA9/MEIS1invoving in activation of the FLT3-LYN signaling axis | 36005562 | [66] |
JMJD1C | JMJD1C aggravates AML malignancy through demethylase-independent upregulation of glycolytic and oxidative associated genes in HOXA9-dependent AML, JMJD1C coexpressed and interacted with HOXA9 | 30622285 | |
PRMT5 | PRMT5 is recruited to the promoter of E-selectin, HOXA9 is transiently bind to their cognate recognition sequence, and induces the symmetric dimethylation of HOXA9 at Arg140, which is crucial for the induction of E-selectin | 22269951 | [71] |
Smad4 | HOXA9 interacted with Smad4 in the cytoplasmic and protected the transformation of normal HSPCs induced by HOXA9, and ruined their interaction with truncated Smad4 leads to the increasing of its target genes such as p15, p21, p27, activates the TGF-β signaling pathway and induces apoptosis in leukemic stem cells(LSCs) | 21471525 | [72] |
G9a | G9a facilitated the gene expression of HOXA9-dependent in mouse AML cells through interacting with HOXA9 and recruiting to the sites of HOXA9-dependent genes, and G9a inhibition inhibited AML cell proliferation and induced differentiation | 24532712 | [73] |
EIF4E | HOXA9Â promotes the export of cyclin D1 and ornithine decarboxylase (ODC) mRNAs in the nucleus and increases the translation efficiency of ODC mRNA in the cytoplasm through directly interacting with EIF4E and competing with PRH from EIF4E | 15657436 | [75] |
C/EBPα, Creb1, Stat5 | Immunoprecipitations assay confirmed that other proteins such as C/EBPα, Creb1, and Stat5 also interacted with HOXA9 to increase acetylation and coactivator recruitment, while further deeper mechanisms about the role of these binding partners in human diseases mediated by HOXA9 are required | 22072553 | [76] |