PMID- 19318089 OWN - NLM STAT- MEDLINE DCOM- 20090515 LR - 20161125 IS - 1090-2104 (Electronic) IS - 0006-291X (Linking) VI - 382 IP - 4 DP - 2009 May 15 TI - Upregulation of Beclin-1 expression and phosphorylation of Bcl-2 and p53 are involved in the JNK-mediated autophagic cell death. PG - 726-9 LID - 10.1016/j.bbrc.2009.03.095 [doi] AB - Though the activation of c-Jun NH2-terminal kinase (JNK) has been reported to be essential for autophagic cell death in response to various stressors, the molecular links between JNK activation and autophagic cell death signaling remain elusive. Here we report that, in the JNK-dependent autophagic cell death of HCT116 cells induced by an agonistic single chain variable fragment antibody, HW1, against human death receptor 5 (DR5), JNK activation upregulated Beclin-1 expression and induced Bcl-2 and p53 phosphorylation. Further, the p53-deficient HCT116 cells showed less susceptibility to the HW1-mediated autophagic cell death than the wild type cells, suggesting that JNK-mediated p53 phosphorylation promotes the autophagic cell death. Our results suggest that DR5-stimulated JNK activation and its consequent fluxes into the pro-autophagic signaling pathways contribute to the autophagic cell death in cancer cells. FAU - Park, Kyung-Jin AU - Park KJ AD - Dept. of Molecular Science and Technology, Ajou University, Yeongtong-Gu, Suwon, Republic of Korea. FAU - Lee, Seung-Hyun AU - Lee SH FAU - Lee, Chang-Han AU - Lee CH FAU - Jang, Ji-Young AU - Jang JY FAU - Chung, Junho AU - Chung J FAU - Kwon, Myung-Hee AU - Kwon MH FAU - Kim, Yong-Sung AU - Kim YS LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20090324 PL - United States TA - Biochem Biophys Res Commun JT - Biochemical and biophysical research communications JID - 0372516 RN - 0 (Apoptosis Regulatory Proteins) RN - 0 (BECN1 protein, human) RN - 0 (Beclin-1) RN - 0 (Membrane Proteins) RN - 0 (Proto-Oncogene Proteins c-bcl-2) RN - 0 (Receptors, TNF-Related Apoptosis-Inducing Ligand) RN - 0 (Tumor Suppressor Protein p53) RN - EC 2.7.11.24 (JNK Mitogen-Activated Protein Kinases) SB - IM MH - Apoptosis Regulatory Proteins/*biosynthesis MH - *Autophagy MH - Beclin-1 MH - Cell Line, Tumor MH - Humans MH - JNK Mitogen-Activated Protein Kinases/metabolism MH - Membrane Proteins/*biosynthesis MH - Phosphorylation MH - Proto-Oncogene Proteins c-bcl-2/*metabolism MH - Receptors, TNF-Related Apoptosis-Inducing Ligand/agonists MH - Tumor Suppressor Protein p53/*metabolism MH - Up-Regulation EDAT- 2009/03/26 09:00 MHDA- 2009/05/16 09:00 CRDT- 2009/03/26 09:00 PHST- 2009/03/17 00:00 [received] PHST- 2009/03/17 00:00 [accepted] PHST- 2009/03/26 09:00 [entrez] PHST- 2009/03/26 09:00 [pubmed] PHST- 2009/05/16 09:00 [medline] AID - S0006-291X(09)00573-7 [pii] AID - 10.1016/j.bbrc.2009.03.095 [doi] PST - ppublish SO - Biochem Biophys Res Commun. 2009 May 15;382(4):726-9. doi: 10.1016/j.bbrc.2009.03.095. Epub 2009 Mar 24.