The p63 protein isoform ΔNp63α modulates Y-box binding protein 1 in its subcellular distribution and regulation of cell survival and motility genes.
The Y-box binding protein 1 (YB-1) belongs to the cold-shock domain protein superfamily, one of the most evolutionarily conserved nucleic acid-binding proteins currently known. YB-1 performs a wide variety of cellular functions, including transcriptional and translational regulation, DNA repair, drug resistance, and stress responses to extracellular signals. Inasmuch as the level of YB-1 drastically increases in tumor cells, this protein is considered to be one of the most indicative markers of malignant tumors. Here, we present evidence that ΔNp63α, the predominant p63 protein isoform in squamous epithelia and YB-1, can physically interact. Into the nucleus, ΔNp63α and YB-1 cooperate in PI3KCA gene promoter activation. Moreover, ΔNp63α promotes YB-1 nuclear accumulation thereby reducing the amount of YB-1 bound to its target transcripts such as that encoding the SNAIL1 protein. Accordingly, ΔNp63α enforced expression was associated with a reduction of the level of SNAIL1, a potent inducer of epithelial to mesenchymal transition. Furthermore, ΔNp63α depletion causes morphological change and enhanced formation of actin stress fibers in squamous cancer cells. Mechanistic studies indicate that ΔNp63α affects cell movement and can reverse the increase of cell motility induced by YB-1 overexpression. These data thus suggest that ΔNp63α provides inhibitory signals for cell motility. Deficiency of ΔNp63α gene expression promotes cell mobilization, at least partially, through a YB-1-dependent mechanism.
Department of Structural and Molecular Biology, Istituto Italiano di Tecnologia and Interdisciplinary Research Centre on Biomaterials, University of Naples Federico II, Naples 80126, Italy.
Antonella
A
Di Costanzo
Annaelena
A
Troiano
Orsola
O
di Martino
Andrea
A
Cacace
Carlo F
CF
Natale
Maurizio
M
Ventre
Paolo
P
Netti
Sergio
S
Caserta
Alessandra
A
Pollice
Girolama
G
La Mantia
Viola
V
Calabrò
D021581:Active Transport, Cell Nucleus / Q000235:genetics; D045744:Cell Line, Tumor; D002465:Cell Movement; D002467:Cell Nucleus / Q000235:genetics / Q000378:metabolism*; D002470:Cell Survival / Q000235:genetics; D006801:Humans; D020033:Protein Isoforms; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*; D051840:Y-Box-Binding Protein 1 / Q000235:genetics / Q000378:metabolism*
D020033:Protein Isoforms; C115051:TP63 protein, human; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; D051840:Y-Box-Binding Protein 1; C070856:YBX1 protein, human