2 research outputs found
Analysis of TAp73-Dependent Signaling via Omics Technologies
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 TAp73Ī± in an inducible manner. We found that TAp73Ī±
promoted mitochondrial activity (accumulation of metabolic intermediates
and up-regulation of proteins related to the Krebs cycle), boosted
glutathione homeostasis, increased arginineācitrullineāNO
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 TAp73Ī± 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 TAp73Ī± in the regulation of
cellular metabolism, cell survival, and cell growth
Analysis of TAp73-Dependent Signaling via Omics Technologies
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 TAp73Ī± in an inducible manner. We found that TAp73Ī±
promoted mitochondrial activity (accumulation of metabolic intermediates
and up-regulation of proteins related to the Krebs cycle), boosted
glutathione homeostasis, increased arginineācitrullineāNO
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 TAp73Ī± 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 TAp73Ī± in the regulation of
cellular metabolism, cell survival, and cell growth