Molecular Analysis of the HOXA2-Dependent Degradation of RCHY1.
The homeodomain transcription factor Hoxa2 interacts with the RING-finger type E3 ubiquitin ligase RCHY1 and induces its proteasomal degradation. In this work, we dissected this non-transcriptional activity of Hoxa2 at the molecular level. The Hoxa2-mediated decay of RCHY1 involves both the 19S and 20S proteasome complexes. It relies on both the Hoxa2 homeodomain and C-terminal moiety although no single deletion in the Hoxa2 sequence could disrupt the RCHY1 interaction. That the Hoxa2 homeodomain alone could mediate RCHY1 binding is consistent with the shared ability all the Hox proteins we tested to interact with RCHY1. Nonetheless, the ability to induce RCHY1 degradation although critically relying on the homeodomain is not common to all Hox proteins. This identifies the homeodomain as necessary but not sufficient for what appears to be an almost generic Hox protein activity. Finally we provide evidence that the Hoxa2-induced degradation of RCHY1 is evolutionarily conserved among vertebrates. These data therefore support the hypothesis that the molecular and functional interaction between Hox proteins and RCHY1 is an ancestral Hox property.
From the Animal Molecular and Cellular Biology group (AMCB), Life Sciences Institute (ISV), Université catholique de Louvain, Louvain-la-Neuve, Belgium.
Laure
L
Bridoux
From the Animal Molecular and Cellular Biology group (AMCB), Life Sciences Institute (ISV), Université catholique de Louvain, Louvain-la-Neuve, Belgium.
Noémie
N
Deneyer
From the Animal Molecular and Cellular Biology group (AMCB), Life Sciences Institute (ISV), Université catholique de Louvain, Louvain-la-Neuve, Belgium.
Isabelle
I
Bergiers
From the Animal Molecular and Cellular Biology group (AMCB), Life Sciences Institute (ISV), Université catholique de Louvain, Louvain-la-Neuve, Belgium.
René
R
Rezsohazy
D000818:Animals; D002467:Cell Nucleus / Q000201:enzymology; D047108:Embryonic Development; D004795:Enzyme Stability; D015870:Gene Expression; D018507:Gene Expression Regulation, Developmental; D057809:HEK293 Cells; D006207:Half-Life; D018398:Homeodomain Proteins / Q000737:chemistry / Q000502:physiology*; D006801:Humans; D051379:Mice; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs; D059748:Proteolysis; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism*
C520321:HOXA2 protein, human; D018398:Homeodomain Proteins; C485369:RCHY1 protein, human; D044767:Ubiquitin-Protein Ligases; D046988:Proteasome Endopeptidase Complex; C061553:ATP dependent 26S protease