The BH3-only member Noxa causes apoptosis in melanoma cells by multiple pathways.

Item request has been placed!

Item request cannot be made.

Processing Request

Read Online Read More Add to Saved list

Author(s): Hassan M;Hassan M; Alaoui A; Feyen O; Mirmohammadsadegh A; Essmann F; Tannapfel A; Gulbins E; Schulze-Osthoff K; Hengge UR
Source:
Oncogene [Oncogene] 2008 Jul 31; Vol. 27 (33), pp. 4557-68. Date of Electronic Publication: 2008 Apr 14.
Publication Type:
Journal Article; Research Support, Non-U.S. Gov't
Language:
English

Additional Information
- Source:
  Publisher: Nature Publishing Group Country of Publication: England NLM ID: 8711562 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1476-5594 (Electronic) Linking ISSN: 09509232 NLM ISO Abbreviation: Oncogene Subsets: MEDLINE
- Publication Information:
  Publication: <2002->: Basingstoke : Nature Publishing Group
  Original Publication: Basingstoke, Hampshire, UK : Scientific & Medical Division, MacMillan Press, c1987-
- Subject Terms:
  Apoptosis*/drug effects ; Apoptosis*/genetics ; MAP Kinase Signaling System*/drug effects ; MAP Kinase Signaling System*/genetics; Endoplasmic Reticulum/*metabolism ; Melanoma/*metabolism ; Mitochondria/*metabolism ; Proto-Oncogene Proteins c-bcl-2/*metabolism; Antioxidants/pharmacology ; BH3 Interacting Domain Death Agonist Protein/genetics ; BH3 Interacting Domain Death Agonist Protein/metabolism ; Caspases/genetics ; Caspases/metabolism ; Cell Line, Tumor ; Endoplasmic Reticulum/genetics ; Gene Transfer Techniques ; Humans ; JNK Mitogen-Activated Protein Kinases/genetics ; JNK Mitogen-Activated Protein Kinases/metabolism ; MAP Kinase Kinase Kinase 5/genetics ; MAP Kinase Kinase Kinase 5/metabolism ; Melanoma/genetics ; Melanoma/therapy ; Mitochondria/genetics ; Proto-Oncogene Proteins c-bcl-2/genetics ; RNA Interference ; p38 Mitogen-Activated Protein Kinases/genetics ; p38 Mitogen-Activated Protein Kinases/metabolism
- Abstract:
  The molecular causes for resistance of melanoma to apoptosis are currently only partly understood. In the present study, we examined gene transfer and expression of the proapoptotic BH3-only protein Noxa as an alternative approach to chemotherapy and investigated the molecular mechanisms regulating Noxa-induced apoptosis. Noxa gene transfer caused dysregulation of both mitochondria and, as shown for the first time, also the endoplasmic reticulum, resulting in the accumulation of reactive oxygen species. Interestingly, expression of Noxa not only triggered the classical mitochondrial caspase cascade, but also resulted in the activation of apoptosis signal-regulating kinase1 and its downstream effectors c-Jun N-terminal kinase and p38. The activation of these kinases was abolished by antioxidants. Moreover, inhibition of the kinases by RNA interference or pharmacological inhibitors significantly attenuated Noxa-induced apoptosis. Thus, our data provide evidence for the involvement of multiple pathways in Noxa-induced apoptosis that are triggered at mitochondria and the endoplasmic reticulum, and suggest Noxa gene transfer as a complementary approach to chemotherapy.
- Comments:
  Erratum in: Oncogene. 2011 Apr 28;30(17):2086.
- Accession Number:
  0 (Antioxidants)
  0 (BH3 Interacting Domain Death Agonist Protein)
  0 (BID protein, human)
  0 (PMAIP1 protein, human)
  0 (Proto-Oncogene Proteins c-bcl-2)
  EC 2.7.11.24 (JNK Mitogen-Activated Protein Kinases)
  EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases)
  EC 2.7.11.25 (MAP Kinase Kinase Kinase 5)
  EC 3.4.22.- (Caspases)
- Publication Date:
  Date Created: 20080415 Date Completed: 20080819 Latest Revision: 20110620
- Publication Date:
  20231215
- Accession Number:
  10.1038/onc.2008.90
- Accession Number:
  18408751

Comments

No Comments.