TY - JOUR
T1 - Downregulation of ΔNp63α in keratinocytes by p14 ARF-mediated SUMO-conjugation and degradation
AU - Vivo, Maria
AU - Di Costanzo, Antonella
AU - Fortugno, Paola
AU - Pollice, Alessandra
AU - Calabrò, Viola
AU - La Mantia, Girolama
PY - 2009/11/1
Y1 - 2009/11/1
N2 - The tumor suppressor p14ARF inhibits cell growth in response to oncogenic stress in a p53-dependent and independent manner. However, new physiologic roles for ARF activation have been proposed. We have previously demonstrated that ARF interacts with p63, influencing its transcriptional activity. p63 is a member of the p53 family involved in skin and limb development, as well as in the homeostasis of mature epidermis. Here, we show that, in human keratinocytes, as well as in tumor-derived cell lines, ARF targets ΔNp63α, the most abundantly expressed p63 isoform, to proteasomal degradation by stimulating its sumoylation. Interestingly, we have observed an increase of ARF expression in differentiating keratinocytes, that is concomitant to the already described upregulation of SUMO2/3. Remarkably, we found that ΔNp63α is preferentially sumoylated by SUMo2, instead of SUMo1, and p14ARF increases the efficiency of this process.
AB - The tumor suppressor p14ARF inhibits cell growth in response to oncogenic stress in a p53-dependent and independent manner. However, new physiologic roles for ARF activation have been proposed. We have previously demonstrated that ARF interacts with p63, influencing its transcriptional activity. p63 is a member of the p53 family involved in skin and limb development, as well as in the homeostasis of mature epidermis. Here, we show that, in human keratinocytes, as well as in tumor-derived cell lines, ARF targets ΔNp63α, the most abundantly expressed p63 isoform, to proteasomal degradation by stimulating its sumoylation. Interestingly, we have observed an increase of ARF expression in differentiating keratinocytes, that is concomitant to the already described upregulation of SUMO2/3. Remarkably, we found that ΔNp63α is preferentially sumoylated by SUMo2, instead of SUMo1, and p14ARF increases the efficiency of this process.
KW - Keratinocyte differentiation
KW - p14ARF
KW - p63
KW - Protein degradation
KW - Sumoylation
UR - http://www.scopus.com/inward/record.url?scp=70449713412&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=70449713412&partnerID=8YFLogxK
M3 - Article
C2 - 19829080
AN - SCOPUS:70449713412
VL - 8
SP - 3545
EP - 3551
JO - Cell Cycle
JF - Cell Cycle
SN - 1538-4101
IS - 21
ER -