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

Forskningsoutput: TidskriftsbidragArtikel i vetenskaplig tidskrift

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.

Detaljer

Författare
Enheter & grupper
Externa organisationer
  • Emory University
  • University of Copenhagen
  • University of Naples Federico II
  • SDN IRCCS
  • CEINGE Biotecnologie Avanzate s.c.a r.l.
Forskningsområden

Ämnesklassifikation (UKÄ) – OBLIGATORISK

  • Cancer och onkologi
Originalspråkengelska
Artikelnummer458
TidskriftCell Death and Disease
Volym9
Utgivningsnummer5
StatusPublished - 2018 jan 1
PublikationskategoriForskning
Peer review utfördJa