Caspase-3-mediated cleavage of the NF-kappa B subunit p65 at the NH2 terminus potentiates naphthoquinone analog-induced apoptosis

The Journal of Biological Chemistry
K H KangK H Choi

Abstract

The transcription factor nuclear factor kappaB (NF-kappaB) plays a crucial role in immune and inflammatory response, and protects cells from apoptosis. In this report, we investigate whether the NF-kappaB signaling pathway is blocked during apoptosis induced by 2,3-dichloro-5,8-dihydroxy-1,4-naphthoquinone (NA), an analog of naphthoquinone. It is observed that NA triggers apoptotic cell death in HeLa cells and destroys resistance to apoptosis caused by tumor necrosis factor-alpha. Data presented in this study establish that p65/RelA, a subunit of NF-kappaB, is cleaved at Asp(97) by caspase-3 during apoptosis. Caspase-3-cleaved p65 loses transcriptional activity and potentiates NA-induced apoptosis, in contrast to an uncleavable mutant of p65, which protects the cell from apoptosis. Caspase-3, which is responsible for the cleavage of p65, is activated via the cytochrome c/caspase-9 signaling pathway rather than Fas/caspase-8 pathway during NA-induced apoptosis. Our results suggest that NA induces apoptosis by the negative regulation of cell survival through caspase-3-mediated cleavage of p65.

References

Nov 10, 1995·Archives of Biochemistry and Biophysics·C S PereraC J McClain
Nov 24, 1995·The Journal of Biological Chemistry·Y NishikawaS Naganathan
Aug 12, 1994·Science·E Kopp, S Ghosh
Apr 16, 1996·Proceedings of the National Academy of Sciences of the United States of America·J M GriscavageL J Ignarro
Oct 4, 1996·Cell·P A Baeuerle, D Baltimore
Nov 1, 1996·Science·D J Van AntwerpI M Verma
Sep 18, 1997·Proceedings of the National Academy of Sciences of the United States of America·Z L ChuD W Ballard
Apr 1, 1997·Seminars in Cancer Biology·M J May, S Ghosh
May 23, 1998·Annual Review of Immunology·S GhoshE B Kopp
Aug 28, 1998·Science·A Ashkenazi, V M Dixit
Aug 28, 1998·Science·D R Green, J C Reed
Jan 5, 1999·Bioorganic & Medicinal Chemistry Letters·S W HamK H Choi
Jan 23, 1999·Oncogene·G NuñezN Inohara

❮ Previous
Next ❯

Citations

Jun 6, 2003·Archives of Pharmacal Research·Hae Jong KimMie Young Kim
Jan 27, 2005·Cancer Chemotherapy and Pharmacology·F PajonkB Fiebich
Jul 23, 2005·Clinical & Experimental Metastasis·J Milburn JessupL M Laguinge
Dec 11, 2002·Current Opinion in Cell Biology·Alicia Algeciras-SchimnichMarcus E Peter
Jan 11, 2013·Cell Death & Disease·T C JacksonP M Kochanek
Dec 2, 2010·Cell Research·Jens StaalRudi Beyaert
Dec 5, 2006·BMC Medicine·Frank PajonkBernd Fiebich
Mar 8, 2013·PLoS Pathogens·Daniela S SilvaNuno M S dos Santos
Oct 12, 2014·BMC Cell Biology·Asif Khurshid QaziAbid Hamid
Jun 27, 2006·The Annals of Thoracic Surgery·Zhenfa ZhangChangli Wang
Aug 27, 2013·The Journal of Surgical Research·Yun-peng WangXin Ma
Jun 6, 2015·Progress in Neuro-psychopharmacology & Biological Psychiatry·Benjamin Keller, Jesús A García-Sevilla
Sep 20, 2005·Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association·Tian-Jye HsiehChing-Hsein Chen
Apr 3, 2008·European Journal of Immunology·David J GregoryMartin Olivier
Apr 23, 2005·The Journal of Biological Chemistry·Nickolay NeznanovAndrei V Gudkov
Mar 9, 2004·The Journal of Immunology : Official Journal of the American Association of Immunologists·Mark V ThorntonJames H Finke
Dec 24, 2009·American Journal of Physiology. Endocrinology and Metabolism·Diana Choi, Minna Woo
Mar 29, 2019·Frontiers in Immunology·Maureen H V FernandesDiego G Diel
Mar 22, 2005·The Journal of Immunology : Official Journal of the American Association of Immunologists·Denise M RayRichard P Phipps
May 7, 2020·Current Cancer Drug Targets·Mamta KumariPiyong Sola

❮ Previous
Next ❯

Related Concepts

Related Feeds

Apoptotic Caspases

Apoptotic caspases belong to the protease enzyme family and are known to play an essential role in inflammation and programmed cell death. Here is the latest research.

ASBMB Publications

The American Society for Biochemistry and Molecular Biology (ASBMB) includes the Journal of Biological Chemistry, Molecular & Cellular Proteomics, and the Journal of Lipid Research. Discover the latest research from ASBMB here.

Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis