Mcl-1128–350 fragment induces apoptosis through direct interaction with Bax

Ménoret, Emmanuelle; Gomez-Bougie, Patricia; Surget, Sylvanie; Trichet, Valérie; Oliver, Lisa; Pellat-Deceunynck, Catherine; Amiot, Martine

doi:10.1016/j.febslet.2009.11.094

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Volume 584, Issue 3 , Pages 487-492, 5 February 2010

Mcl-1^128–350 fragment induces apoptosis through direct interaction with Bax

Edited by Gianni Cesareni

Emmanuelle Ménoret
- INSERM, UMR892, CRCNA, Institut de Recherche thérapeutique de l’Université de Nantes, 44007 Nantes Cedex1, France
- Equipe labellisée Ligue Nationale contre le Cancer 2008, Institut de Recherche thérapeutique de l’Université de Nantes, 44007 Nantes Cedex1, France
Patricia Gomez-Bougie
- INSERM, UMR892, CRCNA, Institut de Recherche thérapeutique de l’Université de Nantes, 44007 Nantes Cedex1, France
- Equipe labellisée Ligue Nationale contre le Cancer 2008, Institut de Recherche thérapeutique de l’Université de Nantes, 44007 Nantes Cedex1, France
- CHU Nantes, Nantes F-44000, France
Sylvanie Surget
- INSERM, UMR892, CRCNA, Institut de Recherche thérapeutique de l’Université de Nantes, 44007 Nantes Cedex1, France
- Equipe labellisée Ligue Nationale contre le Cancer 2008, Institut de Recherche thérapeutique de l’Université de Nantes, 44007 Nantes Cedex1, France
Valérie Trichet
- INSERM, U957, Université de Nantes, Nantes F-44035, France
Lisa Oliver
- INSERM, UMR892, CRCNA, Institut de Recherche thérapeutique de l’Université de Nantes, 44007 Nantes Cedex1, France
- CHU Nantes, Nantes F-44000, France
Catherine Pellat-Deceunynck
- INSERM, UMR892, CRCNA, Institut de Recherche thérapeutique de l’Université de Nantes, 44007 Nantes Cedex1, France
- Equipe labellisée Ligue Nationale contre le Cancer 2008, Institut de Recherche thérapeutique de l’Université de Nantes, 44007 Nantes Cedex1, France
Martine Amiot
- INSERM, UMR892, CRCNA, Institut de Recherche thérapeutique de l’Université de Nantes, 44007 Nantes Cedex1, France
- Equipe labellisée Ligue Nationale contre le Cancer 2008, Institut de Recherche thérapeutique de l’Université de Nantes, 44007 Nantes Cedex1, France
- Corresponding author. Address: U892, Institut de Recherche Thérapeutique de l’Université de Nantes, 8, quai Moncousu, BP 70721, 44007 Nantes, France. Fax: +33 2 28 08 03 29.

Received 13 October 2009; received in revised form 26 November 2009; accepted 27 November 2009. published online 07 December 2009.

Abstract

Mcl-1 full-length (Mcl-1^1–350), a tightly regulated protein, plays an important role in protecting cells against apoptosis. Cleavage of Mcl-1 at Asp127 by caspase (Mcl-1^C1) contributes to the regulation of Mcl-1 expression, but its pro-apoptotic function remains controversial. Here, we reported that Mcl-1^128–350 expression induced caspase-dependent apoptosis. We demonstrated that Mcl-1^128–350 but not Mcl-1^1–350 interacts with Bax. This interaction required an intact BH3 Mcl-1^128–350 domain and leads to Bax activation and translocation to mitochondria. The silencing of Bax, but not of Bak, prevented Mcl-1^128–350 induced apoptosis. In conclusion, Mcl-1^128–350 exerts a pro-apoptotic function governed by its capacity to interact with Bax.

Structured summary

MINT-7306752: Mcl-1 (uniprotkb:Q07820) physically interacts (MI:0915) with BAK (uniprotkb:Q16611) by anti tag coimmunoprecipitation (MI:0007)

MINT-7306728: Mcl-1 (uniprotkb:Q07820) physically interacts (MI:0914) with BAX (uniprotkb:Q07812) and BAK (uniprotkb:Q16611) by anti tag coimmunoprecipitation (MI:0007)

MINT-7307171: F1 ATPase (uniprotkb:Q5TC12), Mcl-1 (uniprotkb:Q07820) and BAX (uniprotkb:Q07812) colocalize (MI:0403) by cosedimentation through density gradients (MI:0029)

Abbreviations: DMEM, Dulbecco’s modified Eagle medium, HEPES, 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid, PEST, proline-, glutamic acid-, serine-, and threonine rich, SDS, sodium dodecyl sulfate, siRNA, small interfering RNA, z-VAD-fmk, benzoyloxycarbonyl-VAD-fluoromethyl ketone, z-LEHD-fmk, benzoyloxycarbonyl-LEHD-fluoromethyl ketone