Mcl-1(128-350) fragment induces apoptosis through direct interaction with Bax.
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.
Ménoret
Emmanuelle
E
INSERM, UMR892, CRCNA, Institut de Recherche thérapeutique de l'Université de Nantes, 44007 Nantes Cedex1, France.
Gomez-Bougie
Patricia
P
Surget
Sylvanie
S
Trichet
Valérie
V
Oliver
Lisa
L
Pellat-Deceunynck
Catherine
C
Amiot
Martine
M
D017209:Apoptosis / Q000235:genetics / Q000502:physiology*; D015153:Blotting, Western; D002460:Cell Line; D045744:Cell Line, Tumor; D006801:Humans; D047468:Immunoprecipitation; D008928:Mitochondria / Q000378:metabolism; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D010957:Plasmids; D011485:Protein Binding; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D050998:bcl-2 Homologous Antagonist-Killer Protein / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000235:genetics / Q000378:metabolism*
D064549:Myeloid Cell Leukemia Sequence 1 Protein; D019253:Proto-Oncogene Proteins c-bcl-2; D050998:bcl-2 Homologous Antagonist-Killer Protein; D051028:bcl-2-Associated X Protein