TY - JOUR
T1 - Analysis of TAp73-dependent signaling via omics technologies
AU - D'Alessandro, Angelo
AU - Marrocco, Cristina
AU - Rinalducci, Sara
AU - Peschiaroli, Angelo
AU - Timperio, Anna Maria
AU - Bongiorno-Borbone, Lucilla
AU - Finazzi Agrò, Alessandro
AU - Melino, Gerry
AU - Zolla, Lello
PY - 2013/9/6
Y1 - 2013/9/6
N2 - Transactivation-proficient (TA) p73 is a transcription factor belonging to the p53 family, which regulates a variety of biological processes, including neurogenesis, differentiation, apoptosis, and DNA damage checkpoint response. In the present study, we adopted multiple Omics approaches, based upon the simultaneous application of metabolomics, lipidomics, and proteomics, in order to dissect the intracellular pathways activated by p73. As cellular model, we utilized a clone of the human osteosarcoma SAOS-2 cell line that allows the expression of TAp73α in an inducible manner. We found that TAp73α promoted mitochondrial activity (accumulation of metabolic intermediates and up-regulation of proteins related to the Krebs cycle), boosted glutathione homeostasis, increased arginine-citrulline-NO metabolism, altered purine synthesis, and promoted the pentose phosphate pathway toward NADPH accumulation for reducing and biosynthetic purposes. Indeed, lipid metabolism was driven toward the accumulation and oxidation of long-chain fatty acids with pro-apoptotic potential. In parallel, the expression of TAp73α was accompanied by the dephosphorylation of key proteins of the mitotic spindle assembly checkpoint. In conclusion, the obtained results confirm existing evidence from transcriptomics analyses and suggest a role for TAp73α in the regulation of cellular metabolism, cell survival, and cell growth.
AB - Transactivation-proficient (TA) p73 is a transcription factor belonging to the p53 family, which regulates a variety of biological processes, including neurogenesis, differentiation, apoptosis, and DNA damage checkpoint response. In the present study, we adopted multiple Omics approaches, based upon the simultaneous application of metabolomics, lipidomics, and proteomics, in order to dissect the intracellular pathways activated by p73. As cellular model, we utilized a clone of the human osteosarcoma SAOS-2 cell line that allows the expression of TAp73α in an inducible manner. We found that TAp73α promoted mitochondrial activity (accumulation of metabolic intermediates and up-regulation of proteins related to the Krebs cycle), boosted glutathione homeostasis, increased arginine-citrulline-NO metabolism, altered purine synthesis, and promoted the pentose phosphate pathway toward NADPH accumulation for reducing and biosynthetic purposes. Indeed, lipid metabolism was driven toward the accumulation and oxidation of long-chain fatty acids with pro-apoptotic potential. In parallel, the expression of TAp73α was accompanied by the dephosphorylation of key proteins of the mitotic spindle assembly checkpoint. In conclusion, the obtained results confirm existing evidence from transcriptomics analyses and suggest a role for TAp73α in the regulation of cellular metabolism, cell survival, and cell growth.
KW - lipidomics
KW - metabolomics
KW - p73
KW - proteomics
UR - http://www.scopus.com/inward/record.url?scp=84883804622&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84883804622&partnerID=8YFLogxK
U2 - 10.1021/pr4005508
DO - 10.1021/pr4005508
M3 - Article
C2 - 23919926
AN - SCOPUS:84883804622
VL - 12
SP - 4207
EP - 4220
JO - Journal of Proteome Research
JF - Journal of Proteome Research
SN - 1535-3893
IS - 9
ER -