Analysis of TAp73-Dependent Signaling via Omics Technologies
Angelo D’Alessandro
Cristina Marrocco
Sara Rinalducci
Angelo Peschiaroli
Anna Maria Timperio
Lucilla Bongiorno-Borbone
Alessandro Finazzi
Agrò
Gerry Melino
Lello Zolla
10.1021/pr4005508.s003
https://acs.figshare.com/articles/dataset/Analysis_of_TAp73_Dependent_Signaling_via_Omics_Technologies/2380723
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.
2013-09-06 00:00:00
pentose phosphate pathway
Omic
SAOS
accumulation
mitotic spindle assembly checkpoint
DNA damage checkpoint response
expression
TAp 73α
metabolism
NADPH
protein
p 53 family