Regulatory effects of sestrin 3 (SESN3) in BCR-ABL expressing cells.

Chronic myeloid leukemia (CML) and Ph+ acute lymphoblastic leukemia (ALL) are characterized by the presence of the BCR-ABL oncoprotein, which leads to activation of a plethora of pro-mitogenic and pro-survival pathways, including the mTOR signaling cascade. We provide evidence that in BCR-ABL expres...

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Autores principales:	Eliza Vakana, Ahmet Dirim Arslan, Amy Szilard, Jessica K Altman, Leonidas C Platanias
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/24052efa13034cfc8650dcc815e472d7
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spelling	oai:doaj.org-article:24052efa13034cfc8650dcc815e472d72021-11-18T08:45:49ZRegulatory effects of sestrin 3 (SESN3) in BCR-ABL expressing cells.1932-620310.1371/journal.pone.0078780https://doaj.org/article/24052efa13034cfc8650dcc815e472d72013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24260131/?tool=EBIhttps://doaj.org/toc/1932-6203Chronic myeloid leukemia (CML) and Ph+ acute lymphoblastic leukemia (ALL) are characterized by the presence of the BCR-ABL oncoprotein, which leads to activation of a plethora of pro-mitogenic and pro-survival pathways, including the mTOR signaling cascade. We provide evidence that in BCR-ABL expressing cells, treatment with tyrosine kinase inhibitors (TKIs) results in upregulation of mRNA levels and protein expression of sestrin3 (SESN3), a unique cellular inhibitor of mTOR complex 1 (mTORC1). Such upregulation appears to be mediated by regulatory effects on mTOR, as catalytic inhibition of the mTOR kinase also induces SESN3. Catalytic mTOR inhibition also results in upregulation of SESN3 expression in cells harboring the TKI-insensitive T315I-BCR-ABL mutant, which is resistant to imatinib mesylate. Overexpression of SESN3 results in inhibitory effects on different Ph+ leukemic cell lines including KT-1-derived leukemic precursors, indicating that SESN3 mediates anti-leukemic responses in Ph+ cells. Altogether, our findings suggest the existence of a novel mechanism for the generation of antileukemic responses in CML cells, involving upregulation of SESN3 expression.Eliza VakanaAhmet Dirim ArslanAmy SzilardJessica K AltmanLeonidas C PlataniasPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 11, p e78780 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Eliza Vakana Ahmet Dirim Arslan Amy Szilard Jessica K Altman Leonidas C Platanias Regulatory effects of sestrin 3 (SESN3) in BCR-ABL expressing cells.
description	Chronic myeloid leukemia (CML) and Ph+ acute lymphoblastic leukemia (ALL) are characterized by the presence of the BCR-ABL oncoprotein, which leads to activation of a plethora of pro-mitogenic and pro-survival pathways, including the mTOR signaling cascade. We provide evidence that in BCR-ABL expressing cells, treatment with tyrosine kinase inhibitors (TKIs) results in upregulation of mRNA levels and protein expression of sestrin3 (SESN3), a unique cellular inhibitor of mTOR complex 1 (mTORC1). Such upregulation appears to be mediated by regulatory effects on mTOR, as catalytic inhibition of the mTOR kinase also induces SESN3. Catalytic mTOR inhibition also results in upregulation of SESN3 expression in cells harboring the TKI-insensitive T315I-BCR-ABL mutant, which is resistant to imatinib mesylate. Overexpression of SESN3 results in inhibitory effects on different Ph+ leukemic cell lines including KT-1-derived leukemic precursors, indicating that SESN3 mediates anti-leukemic responses in Ph+ cells. Altogether, our findings suggest the existence of a novel mechanism for the generation of antileukemic responses in CML cells, involving upregulation of SESN3 expression.
format	article
author	Eliza Vakana Ahmet Dirim Arslan Amy Szilard Jessica K Altman Leonidas C Platanias
author_facet	Eliza Vakana Ahmet Dirim Arslan Amy Szilard Jessica K Altman Leonidas C Platanias
author_sort	Eliza Vakana
title	Regulatory effects of sestrin 3 (SESN3) in BCR-ABL expressing cells.
title_short	Regulatory effects of sestrin 3 (SESN3) in BCR-ABL expressing cells.
title_full	Regulatory effects of sestrin 3 (SESN3) in BCR-ABL expressing cells.
title_fullStr	Regulatory effects of sestrin 3 (SESN3) in BCR-ABL expressing cells.
title_full_unstemmed	Regulatory effects of sestrin 3 (SESN3) in BCR-ABL expressing cells.
title_sort	regulatory effects of sestrin 3 (sesn3) in bcr-abl expressing cells.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/24052efa13034cfc8650dcc815e472d7
work_keys_str_mv	AT elizavakana regulatoryeffectsofsestrin3sesn3inbcrablexpressingcells AT ahmetdirimarslan regulatoryeffectsofsestrin3sesn3inbcrablexpressingcells AT amyszilard regulatoryeffectsofsestrin3sesn3inbcrablexpressingcells AT jessicakaltman regulatoryeffectsofsestrin3sesn3inbcrablexpressingcells AT leonidascplatanias regulatoryeffectsofsestrin3sesn3inbcrablexpressingcells
_version_	1718421310364712960

Regulatory effects of sestrin 3 (SESN3) in BCR-ABL expressing cells.

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