Conversion of CD95 (Fas) Type II into Type I signaling by sub-lethal doses of cycloheximide

Brumatti, G; Yon, M; Castro, F A; Bueno-da-Silva, A E B; Jacysyn, J F; Brunner, T; Amarante-Mendes, G P (2008). Conversion of CD95 (Fas) Type II into Type I signaling by sub-lethal doses of cycloheximide. Experimental cell research, 314(3), pp. 554-63. San Diego, Calif.: Elsevier 10.1016/j.yexcr.2007.11.003

Full text not available from this repository. (Request a copy)

CD95 (Fas/Apo-1)-mediated apoptosis was shown to occur through two distinct pathways. One involves a direct activation of caspase-3 by large amounts of caspase-8 generated at the DISC (Type I cells). The other is related to the cleavage of Bid by low concentration of caspase-8, leading to the release of cytochrome c from mitochondria and the activation of caspase-3 by the cytochrome c/APAF-1/caspase-9 apoptosome (Type II cells). It is also known that the protein synthesis inhibitor cycloheximide (CHX) sensitizes Type I cells to CD95-mediated apoptosis, but it remains contradictory whether this effect also occurs in Type II cells. Here, we show that sub-lethal doses of CHX render both Type I and Type II cells sensitive to the apoptogenic effect of anti-CD95 antibodies but not to chemotherapeutic drugs. Moreover, Bcl-2-positive Type II cells become strongly sensitive to CD95-mediated apoptosis by the addition of CHX to the cell culture. This is not the result of a restraint of the anti-apoptotic effect of Bcl-2 at the mitochondrial level since CHX-treated Type II cells still retain their resistance to chemotherapeutic drugs. Therefore, CHX treatment is granting the CD95-mediated pathway the ability to bypass the mitochondria requirement to apoptosis, much alike to what is observed in Type I cells.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Service Sector > Institute of Pathology

UniBE Contributor:

Brunner, Thomas

ISSN:

0014-4827

ISBN:

18078929

Publisher:

Elsevier

Language:

English

Submitter:

Factscience Import

Date Deposited:

04 Oct 2013 15:02

Last Modified:

04 May 2014 23:19

Publisher DOI:

10.1016/j.yexcr.2007.11.003

PubMed ID:

18078929

Web of Science ID:

000252832300012

URI:

https://boris.unibe.ch/id/eprint/27077 (FactScience: 101689)

Actions (login required)

Edit item Edit item
Provide Feedback