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

被引：12

作者：

Menoret, Emmanuelle ^{[2
]}

Gomez-Bougie, Patricia ^{[2
,4
]}

Surget, Sylvanie ^{[2
]}

Trichet, Valerie ^{[3
]}

Oliver, Lisa ^{[4
]}

Pellat-Deceunynck, Catherine ^{[2
]}

Amiot, Martine ^{[1
,2
]}

机构：

[1] Univ Nantes, Inst Rech Therapeut, INSERM, CRCNA,UMR892,U892, F-44007 Nantes 1, France

[2] Univ Nantes, Inst Rech Therapeut, Equipe Labellisee Ligue Natl Canc 2008, F-44007 Nantes 1, France

[3] Univ Nantes, INSERM, U957, F-44035 Nantes, France

[4] CHU Nantes, F-44000 Nantes, France

来源：

FEBS LETTERS | 2010年 / 584卷 / 03期

关键词：

Mcl-1; Cleaved Mcl-1; Bax activation; MCL-1; CLEAVAGE; MYELOMA CELLS; CYTOCHROME-C; MEDIATED APOPTOSIS; BH3-ONLY PROTEINS; MULTIPLE-MYELOMA; SURVIVAL; BCL-2; BIM; DIFFERENTIATION;

D O I：

10.1016/j.febslet.2009.11.094

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页码：487 / 492

页数：6

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