title: KPC2 relocalizes HOXA2 to the cytoplasm and decreases its transcriptional activity.
abstract: Regulation of transcription factor activity relies on molecular interactions or enzymatic modifications which influence their interaction with DNA cis-regulatory sequences, their transcriptional activation or repression, and stability or intracellular distribution of these proteins. Regarding the well-conserved Hox protein family, a restricted number of activity regulators have been highlighted thus far. In the framework of a proteome-wide screening aiming at identifying proteins interacting with Hoxa2, KPC2, an adapter protein constitutive of the KPC ubiquitin-ligase complex, was identified. In this work, KPC2 was confirmed as being a genuine interactor of Hoxa2 by co-precipitation and bimolecular fluorescence complementation assays. At functional level, KPC2 diminishes the transcriptional activity and induces the nuclear exit of Hoxa2. Gene expression analyses revealed that Kpc2 is active in restricted areas of the developing mouse embryo which overlap with the Hoxa2 expression domain. Together, our data support that KPC2 regulates Hoxa2 by promoting its relocation to the cytoplasm.
authors: Animal Molecular and Cellular Biology group (AMCB), Life Sciences Institute (ISV), Université catholique de Louvain, Louvain-la-Neuve 1348, Belgium.
authors: Laure
authors: L
authors: Bridoux
authors: Animal Molecular and Cellular Biology group (AMCB), Life Sciences Institute (ISV), Université catholique de Louvain, Louvain-la-Neuve 1348, Belgium.
authors: Isabelle
authors: I
authors: Bergiers
authors: Animal Molecular and Cellular Biology group (AMCB), Life Sciences Institute (ISV), Université catholique de Louvain, Louvain-la-Neuve 1348, Belgium.
authors: Amandine
authors: A
authors: Draime
authors: Animal Molecular and Cellular Biology group (AMCB), Life Sciences Institute (ISV), Université catholique de Louvain, Louvain-la-Neuve 1348, Belgium.
authors: Mathias
authors: M
authors: Halbout
authors: Animal Molecular and Cellular Biology group (AMCB), Life Sciences Institute (ISV), Université catholique de Louvain, Louvain-la-Neuve 1348, Belgium.
authors: Noémie
authors: N
authors: Deneyer
authors: Laboratory of Signaling and Protein Interactions, GIGA- Signal Transduction, Université de Liège, Liège 4000, Belgium.
authors: Jean-Claude
authors: JC
authors: Twizere
authors: Animal Molecular and Cellular Biology group (AMCB), Life Sciences Institute (ISV), Université catholique de Louvain, Louvain-la-Neuve 1348, Belgium. Electronic address: rene.rezsohazy@uclouvain.be.
authors: René
authors: R
authors: Rezsohazy
mesh_terms: D000818:Animals; D003593:Cytoplasm / Q000378:metabolism; D047108:Embryonic Development / Q000235:genetics*; D018507:Gene Expression Regulation, Developmental; D018398:Homeodomain Proteins / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics*; D051379:Mice; D011485:Protein Binding; D015533:Transcriptional Activation / Q000235:genetics*
chemical_list: D018398:Homeodomain Proteins; C489833:Hoxa2 protein, mouse; D047908:Intracellular Signaling Peptides and Proteins; C000603432:KPC2 protein, mouse
keywords: HOX; HOXA2; Interaction; KPC2; Mouse development