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- Title
SHOC2 scaffold protein modulates daunorubicin-induced cell death through p53 modulation in lymphoid leukemia cells.
- Authors
Silveira, Vanessa Silva; Borges, Kleiton Silva; Santos, Verena Silva; Ruckert, Mariana Tannús; Vieira, Gabriela Maciel; Vasconcelos, Elton José Rosas; Nagano, Luis Fernando Peinado; Tone, Luiz Gonzaga; Scrideli, Carlos Alberto
- Abstract
SHOC2 scaffold protein has been mainly related to oncogenic ERK signaling through the RAS-SHOC2-PP1 phosphatase complex. In leukemic cells however, SHOC2 upregulation has been previously related to an increased 5-year event-free survival of pediatric pre-B acute lymphoid leukemia, suggesting that SHOC2 could be a potential prognostic marker. To address such paradoxical function, our study investigated how SHOC2 impact leukemic cells drug response. Our transcriptome analysis has shown that SHOC2 can modulate the DNA-damage mediated by p53. Notably, upon genetic inhibition of SHOC2 we observed a significant impairment of p53 expression, which in turn, leads to the blockage of key apoptotic molecules. To confirm the specificity of DNA-damage related modulation, several anti-leukemic drugs has been tested and we did confirm that the proposed mechanism impairs cell death upon daunorubicin-induced DNA damage of human lymphoid cells. In conclusion, our study uncovers new insights into SHOC2 function and reveals that this scaffold protein may be essential to activate a novel mechanism of p53-induced cell death in pre-B lymphoid cells.
- Subjects
SCAFFOLD proteins; LYMPHOCYTIC leukemia; DNA damage; LEUKEMIA treatment; CELL death
- Publication
Scientific Reports, 2020, Vol 10, Issue 1, pN.PAG
- ISSN
2045-2322
- Publication type
Article
- DOI
10.1038/s41598-020-72124-1