BAP1 induces cell death via interaction with 14-3-3 in neuroblastoma

Wondossen Sime; Qiankun Niu; Yasmin Abassi; Katarzyna Chmielarska Masoumi; Reihaneh Zarrizi; Julie Bonne Køhler; Sven Kjellström; Vito Alessandro Lasorsa; Mario Capasso; Haian Fu; Ramin Massoumi

doi:10.1038/s41419-018-0500-6

BAP1 induces cell death via interaction with 14-3-3 in neuroblastoma

Wondossen Sime, Qiankun Niu, Yasmin Abassi, Katarzyna Chmielarska Masoumi, Reihaneh Zarrizi, Julie Bonne Køhler, Sven Kjellström, Vito Alessandro Lasorsa, Mario Capasso, Haian Fu, Ramin Massoumi^*

^*Corresponding author af dette arbejde

15 Citationer (Scopus)

40 Downloads (Pure)

Abstract

BRCA1-associated protein 1 (BAP1) is a nuclear deubiquitinating enzyme that is associated with multiprotein complexes that regulate key cellular pathways, including cell cycle, cellular differentiation, cell death, and the DNA damage response. In this study, we found that the reduced expression of BAP1 pro6motes the survival of neuroblastoma cells, and restoring the levels of BAP1 in these cells facilitated a delay in S and G2/M phase of the cell cycle, as well as cell apoptosis. The mechanism that BAP1 induces cell death is mediated via an interaction with 14-3-3 protein. The association between BAP1 and 14-3-3 protein releases the apoptotic inducer protein Bax from 14-3-3 and promotes cell death through the intrinsic apoptosis pathway. Xenograft studies confirmed that the expression of BAP1 reduces tumor growth and progression in vivo by lowering the levels of pro-survival factors such as Bcl-2, which in turn diminish the survival potential of the tumor cells. Patient data analyses confirmed the finding that the high-BAP1 mRNA expression correlates with a better clinical outcome. In summary, our study uncovers a new mechanism for BAP1 in the regulation of cell apoptosis in neuroblastoma cells.

Originalsprog	Engelsk
Artikelnummer	458
Tidsskrift	Cell Death and Disease
Vol/bind	9
Udgave nummer	5
Sider (fra-til)	1-16
Antal sider	16
ISSN	2041-4889
DOI	https://doi.org/10.1038/s41419-018-0500-6
Status	Udgivet - 2018

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10.1038/s41419-018-0500-6Licens: CC BY

BAP1 induces cell death via interaction with 14-3-3 in neuroblastomaForlagets udgivne version, 2,29 MBLicens: CC BY

Citationsformater

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title = "BAP1 induces cell death via interaction with 14-3-3 in neuroblastoma",

abstract = "BRCA1-associated protein 1 (BAP1) is a nuclear deubiquitinating enzyme that is associated with multiprotein complexes that regulate key cellular pathways, including cell cycle, cellular differentiation, cell death, and the DNA damage response. In this study, we found that the reduced expression of BAP1 pro6motes the survival of neuroblastoma cells, and restoring the levels of BAP1 in these cells facilitated a delay in S and G2/M phase of the cell cycle, as well as cell apoptosis. The mechanism that BAP1 induces cell death is mediated via an interaction with 14-3-3 protein. The association between BAP1 and 14-3-3 protein releases the apoptotic inducer protein Bax from 14-3-3 and promotes cell death through the intrinsic apoptosis pathway. Xenograft studies confirmed that the expression of BAP1 reduces tumor growth and progression in vivo by lowering the levels of pro-survival factors such as Bcl-2, which in turn diminish the survival potential of the tumor cells. Patient data analyses confirmed the finding that the high-BAP1 mRNA expression correlates with a better clinical outcome. In summary, our study uncovers a new mechanism for BAP1 in the regulation of cell apoptosis in neuroblastoma cells.",

author = "Wondossen Sime and Qiankun Niu and Yasmin Abassi and Masoumi, {Katarzyna Chmielarska} and Reihaneh Zarrizi and K{\o}hler, {Julie Bonne} and Sven Kjellstr{\"o}m and Lasorsa, {Vito Alessandro} and Mario Capasso and Haian Fu and Ramin Massoumi",

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doi = "10.1038/s41419-018-0500-6",

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TY - JOUR

T1 - BAP1 induces cell death via interaction with 14-3-3 in neuroblastoma

AU - Sime, Wondossen

AU - Niu, Qiankun

AU - Abassi, Yasmin

AU - Masoumi, Katarzyna Chmielarska

AU - Zarrizi, Reihaneh

AU - Køhler, Julie Bonne

AU - Kjellström, Sven

AU - Lasorsa, Vito Alessandro

AU - Capasso, Mario

AU - Fu, Haian

AU - Massoumi, Ramin

PY - 2018

Y1 - 2018

N2 - BRCA1-associated protein 1 (BAP1) is a nuclear deubiquitinating enzyme that is associated with multiprotein complexes that regulate key cellular pathways, including cell cycle, cellular differentiation, cell death, and the DNA damage response. In this study, we found that the reduced expression of BAP1 pro6motes the survival of neuroblastoma cells, and restoring the levels of BAP1 in these cells facilitated a delay in S and G2/M phase of the cell cycle, as well as cell apoptosis. The mechanism that BAP1 induces cell death is mediated via an interaction with 14-3-3 protein. The association between BAP1 and 14-3-3 protein releases the apoptotic inducer protein Bax from 14-3-3 and promotes cell death through the intrinsic apoptosis pathway. Xenograft studies confirmed that the expression of BAP1 reduces tumor growth and progression in vivo by lowering the levels of pro-survival factors such as Bcl-2, which in turn diminish the survival potential of the tumor cells. Patient data analyses confirmed the finding that the high-BAP1 mRNA expression correlates with a better clinical outcome. In summary, our study uncovers a new mechanism for BAP1 in the regulation of cell apoptosis in neuroblastoma cells.

AB - BRCA1-associated protein 1 (BAP1) is a nuclear deubiquitinating enzyme that is associated with multiprotein complexes that regulate key cellular pathways, including cell cycle, cellular differentiation, cell death, and the DNA damage response. In this study, we found that the reduced expression of BAP1 pro6motes the survival of neuroblastoma cells, and restoring the levels of BAP1 in these cells facilitated a delay in S and G2/M phase of the cell cycle, as well as cell apoptosis. The mechanism that BAP1 induces cell death is mediated via an interaction with 14-3-3 protein. The association between BAP1 and 14-3-3 protein releases the apoptotic inducer protein Bax from 14-3-3 and promotes cell death through the intrinsic apoptosis pathway. Xenograft studies confirmed that the expression of BAP1 reduces tumor growth and progression in vivo by lowering the levels of pro-survival factors such as Bcl-2, which in turn diminish the survival potential of the tumor cells. Patient data analyses confirmed the finding that the high-BAP1 mRNA expression correlates with a better clinical outcome. In summary, our study uncovers a new mechanism for BAP1 in the regulation of cell apoptosis in neuroblastoma cells.

U2 - 10.1038/s41419-018-0500-6

DO - 10.1038/s41419-018-0500-6

M3 - Journal article

C2 - 29686263

AN - SCOPUS:85045947649

SN - 2041-4889

VL - 9

SP - 1

EP - 16

JO - Cell Death & Disease

JF - Cell Death & Disease

IS - 5

M1 - 458

ER -

BAP1 induces cell death via interaction with 14-3-3 in neuroblastoma

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