SHOC2 scaffold protein modulates daunorubicin-induced cell death through p53 modulation in lymphoid leukemia cells

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, suggestin...

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Autores principales:	Vanessa Silva Silveira, Kleiton Silva Borges, Verena Silva Santos, Mariana Tannús Ruckert, Gabriela Maciel Vieira, Elton José Rosas Vasconcelos, Luis Fernando Peinado Nagano, Luiz Gonzaga Tone, Carlos Alberto Scrideli
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2020
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/70109987fc1b425ba3936d97783b5127
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spelling	oai:doaj.org-article:70109987fc1b425ba3936d97783b51272021-12-02T18:33:51ZSHOC2 scaffold protein modulates daunorubicin-induced cell death through p53 modulation in lymphoid leukemia cells10.1038/s41598-020-72124-12045-2322https://doaj.org/article/70109987fc1b425ba3936d97783b51272020-09-01T00:00:00Zhttps://doi.org/10.1038/s41598-020-72124-1https://doaj.org/toc/2045-2322Abstract 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.Vanessa Silva SilveiraKleiton Silva BorgesVerena Silva SantosMariana Tannús RuckertGabriela Maciel VieiraElton José Rosas VasconcelosLuis Fernando Peinado NaganoLuiz Gonzaga ToneCarlos Alberto ScrideliNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 10, Iss 1, Pp 1-7 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Vanessa Silva Silveira Kleiton Silva Borges Verena Silva Santos Mariana Tannús Ruckert Gabriela Maciel Vieira Elton José Rosas Vasconcelos Luis Fernando Peinado Nagano Luiz Gonzaga Tone Carlos Alberto Scrideli SHOC2 scaffold protein modulates daunorubicin-induced cell death through p53 modulation in lymphoid leukemia cells
description	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.
format	article
author	Vanessa Silva Silveira Kleiton Silva Borges Verena Silva Santos Mariana Tannús Ruckert Gabriela Maciel Vieira Elton José Rosas Vasconcelos Luis Fernando Peinado Nagano Luiz Gonzaga Tone Carlos Alberto Scrideli
author_facet	Vanessa Silva Silveira Kleiton Silva Borges Verena Silva Santos Mariana Tannús Ruckert Gabriela Maciel Vieira Elton José Rosas Vasconcelos Luis Fernando Peinado Nagano Luiz Gonzaga Tone Carlos Alberto Scrideli
author_sort	Vanessa Silva Silveira
title	SHOC2 scaffold protein modulates daunorubicin-induced cell death through p53 modulation in lymphoid leukemia cells
title_short	SHOC2 scaffold protein modulates daunorubicin-induced cell death through p53 modulation in lymphoid leukemia cells
title_full	SHOC2 scaffold protein modulates daunorubicin-induced cell death through p53 modulation in lymphoid leukemia cells
title_fullStr	SHOC2 scaffold protein modulates daunorubicin-induced cell death through p53 modulation in lymphoid leukemia cells
title_full_unstemmed	SHOC2 scaffold protein modulates daunorubicin-induced cell death through p53 modulation in lymphoid leukemia cells
title_sort	shoc2 scaffold protein modulates daunorubicin-induced cell death through p53 modulation in lymphoid leukemia cells
publisher	Nature Portfolio
publishDate	2020
url	https://doaj.org/article/70109987fc1b425ba3936d97783b5127
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SHOC2 scaffold protein modulates daunorubicin-induced cell death through p53 modulation in lymphoid leukemia cells

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