The Homeodomain Transcription Factor Hoxa2 Interacts with and Promotes the Proteasomal Degradation of the E3 Ubiquitin Protein Ligase RCHY1

Bergiers, Isabelle; Bridoux, Laure; Nguyen, Nathan; Twizere, Jean-Claude; Rezsöhazy, René

doi:10.1371/journal.pone.0080387

Cited by 19 publications

(24 citation statements)

References 74 publications

(97 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Alternate mechanisms have been described for other HOX proteins as well. For example, Hoxa2 can indirectly stabilize p53 by binding to p53’s E3 ubiquitin ligase, RCHY1, leading to the degradation of RCHY1 (155). Hoxa7 and Hoxa14 can bind to the initiation factor eIF4E in liver cancer, potentially affecting the nuclear transport of eIF4E-dependent transcripts like c-myc, fgf2, vegf , ornithine decarboxylase and cyclin-D1 (156).…”

Section: Transcriptional Targets Of Hoxa9mentioning

confidence: 99%

Role of HOXA9 in leukemia: dysregulation, cofactors and essential targets

2015

View full text Add to dashboard Cite

HOXA9 is a homeodomain-containing transcription factor that plays an important role in hematopoietic stem cell expansion and is commonly deregulated in acute leukemias. A variety of upstream genetic alterations in acute myeloid leukemia (AML) lead to overexpression of HOXA9, which is a strong predictor of poor prognosis. In many cases, HOXA9 has been shown to be necessary for maintaining leukemic transformation, however the molecular mechanisms through which it promotes leukemogenesis remain elusive. Recent work has established that HOXA9 regulates downstream gene expression through binding at promoter distal enhancers along with a subset of cell-specific cofactor and collaborator proteins. Increasing efforts are being made to identify both the critical cofactors and target genes required for maintaining transformation in HOXA9-overexpressing leukemias. With continued advances in understanding HOXA9-mediated transformation, there is a wealth of opportunity for developing novel therapeutics that would be applicable for the greater than 50% of AML with overexpression of HOXA9.

show abstract

Section: Transcriptional Targets Of Hoxa9mentioning

confidence: 99%

Role of HOXA9 in leukemia: dysregulation, cofactors and essential targets

2015

View full text Add to dashboard Cite

show abstract

“…Protein degradation. Hox proteins control the formation and activity of E3 ubiquitin ligase complexes: Hoxb4 and Hoxa9 promote geminin degradation (Ohno et al, 2013(Ohno et al, , 2010; HOXB13 interacts with cyclin D1 and promotes its degradation (Hamid et al, 2014); HOXA2 interacts with the E3 ubiquitin ligase RCHY1 and promotes its proteasome-mediated decay (Bergiers et al, 2013); HOXC10 interacts with CDC27, a core subunit of the anaphase-promoting complex (APC), an E3 ubiquitin ligase complex that is involved in mitosis exit (Gabellini et al, 2003).…”

Section: An Overview Of the Hox Gene Familymentioning

confidence: 99%

Cellular and molecular insights into Hox protein action

et al. 2015

View full text Add to dashboard Cite

Hox genes encode homeodomain transcription factors that control morphogenesis and have established functions in development and evolution. Hox proteins have remained enigmatic with regard to the molecular mechanisms that endow them with specific and diverse functions, and to the cellular functions that they control. Here, we review recent examples of Hox-controlled cellular functions that highlight their versatile and highly context-dependent activity. This provides the setting to discuss how Hox proteins control morphogenesis and organogenesis. We then summarise the molecular modalities underlying Hox protein function, in particular in light of current models of transcription factor function. Finally, we discuss how functional divergence between Hox proteins might be achieved to give rise to the many facets of their action.

show abstract

“…2015 PubMed PMID: 26303204), human HOXA3 and HOXC4 (http://horfdb.dfci.harvard.edu/hv7/) were used to generate mammalian expression vectors for FLAG-HOX (v1899 destination vector) using the gateway technology (Barrios-Rodiles et al, 2005). Gateway® expression vectors for pExpFLAG-Hoxa1 and pExpFLAG-Hoxa2 are described in (Bergiers et al, 2013; Lambert et al, 2012). HEK293 cells were grown at 37°C, in a humidified atmosphere with 5% CO2 in DMEM (D6429) supplemented with 10% FBS, 5% penicillin/streptomycin, and 5% L-glutamine.…”

Section: Methodsmentioning

confidence: 99%

HOX paralogs selectively convert binding of ubiquitous transcription factors into tissue-specific patterns of enhancer activation

Bridoux

Zarrineh

Mallen

et al. 2019

Preprint

Self Cite

View full text Add to dashboard Cite

19Gene expression programs determine cell fate in embryonic development and their 20 dysregulation results in disease. Transcription factors (TFs) control gene expression by 21 binding to enhancers, but how TFs select and activate their target enhancers is still unclear. 22HOX TFs share conserved homeodomains with highly similar sequence recognition 23properties, yet they impart the identity of different animal body parts. To understand how 24 HOX TFs control their specific transcriptional programs in vivo, we compared HOXA2 and 25 HOXA3 binding profiles in the mouse embryo. HOXA2 and HOXA3 directly cooperate with 26 TALE TFs and selectively target different subsets of a broad TALE chromatin platform. 27Binding of HOX and tissue-specific TFs convert low affinity TALE binding into high 28 confidence, tissue-specific binding events, which bear the mark of active enhancers. We 29 propose that HOX paralogs, alone and in combination with tissue-specific TFs, generate 30 tissue-specific transcriptional outputs by modulating the activity of TALE TFs at selected 31 enhancers. 32 33 Introduction 34 Gene expression programs instruct and maintain cell fate in embryonic development and 35 adult tissue homeostasis. Transcription factors (TFs) control gene expression by binding to 36 enhancers (Reiter et al., 2017; Spitz and Furlong, 2012). However, we still have no clear 37 idea of how TFs select their precise sets of target enhancers. While TFs contain DNA 38 binding domains which recognize DNA in a sequence-specific manner, these interactions 39 are typically insufficient to direct a TF to its functional targets. 40Transcriptional regulation is mediated by TFs working together, rather than in isolation. The 41 widespread occurrence of collaborative TF binding is imposed by chromatin. A single TF 42 cannot easily compete with nucleosomes to access DNA, but multiple TFs that recognize 43 closely spaced binding sites can effectively displace nucleosomes and indirectly facilitate 44 each other's binding (Mirny, 2010; Moyle-Heyrman et al., 2011). Such indirect cooperativity 45 can also result in TFs recognizing low affinity sites, i.e. sites that deviate from their optimal 46 3 consensus in vitro (Farley et al., 2015). Recent observations indicate that TF cooperativity 47 does not end at binding enhancers: clusters of enhancer-bound TFs concentrate co-48 activators and other nuclear factors via dynamic fuzzy interactions, driven by their 49 intrinsically disordered regions (IDRs). IDRs function in molecular recognition and mediate 50 the interaction with a diversity of regulatory proteins (Cumberworth et al., 2013; Staby et al., 51 2017) to promote the liquid-liquid phase transition associated with gene activation (Boija et 52 al., 2018). Thus, the formation, on DNA segments, of regulatory complexes made of different 53 combinations of factors, is key to activation of gene expression. These distinct combinations 54 of TFs produce virtually inexhaustible flavours of gene expression and cell fate (Spitz and 55 Furlong, 2012).56...

show abstract

The Homeodomain Transcription Factor Hoxa2 Interacts with and Promotes the Proteasomal Degradation of the E3 Ubiquitin Protein Ligase RCHY1

Cited by 19 publications

References 74 publications

Role of HOXA9 in leukemia: dysregulation, cofactors and essential targets

Role of HOXA9 in leukemia: dysregulation, cofactors and essential targets

Cellular and molecular insights into Hox protein action

HOX paralogs selectively convert binding of ubiquitous transcription factors into tissue-specific patterns of enhancer activation

Contact Info

Product

Resources

About