The homeodomain transcription factor Hoxa2 interacts with and promotes the proteasomal degradation of the E3 ubiquitin protein ligase RCHY1.
Hox proteins are conserved homeodomain transcription factors known to be crucial regulators of animal development. As transcription factors, the functions and modes of action (co-factors, target genes) of Hox proteins have been very well studied in a multitude of animal models. However, a handful of reports established that Hox proteins may display molecular activities distinct from gene transcription regulation. Here, we reveal that Hoxa2 interacts with 20S proteasome subunits and RCHY1 (also known as PIRH2), an E3 ubiquitin ligase that targets p53 for degradation. We further show that Hoxa2 promotes proteasome-dependent degradation of RCHY1 in an ubiquitin-independent manner. Correlatively, Hoxa2 alters the RCHY1-mediated ubiquitination of p53 and promotes p53 stabilization. Together, our data establish that Hoxa2 can regulate the proteasomal degradation of RCHY1 and stabilization of p53.
Molecular and Cellular Animal Embryology Group, Life Sciences Institute, Université catholique de Louvain, Louvain-la-Neuve, Belgium.
Isabelle
I
Bergiers
Laure
L
Bridoux
Nathan
N
Nguyen
Jean-Claude
JC
Twizere
René
R
Rezsöhazy
D002460:Cell Line; D018398:Homeodomain Proteins / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D011485:Protein Binding; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism*; D054875:Ubiquitination
C520321:HOXA2 protein, human; D018398:Homeodomain Proteins; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; C485369:RCHY1 protein, human; D044767:Ubiquitin-Protein Ligases; C488165:PSMA3 protein, human; C561469:PSMB2 protein, human; D046988:Proteasome Endopeptidase Complex