title: Mcl-1(128-350) fragment induces apoptosis through direct interaction with Bax.
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.
authors.affiliation: INSERM, UMR892, CRCNA, Institut de Recherche thérapeutique de l'Université de Nantes, 44007 Nantes Cedex1, France.
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Ménoret
authors.forename: Patricia
authors.initials: P
authors.lastname: Gomez-Bougie
authors.forename: Sylvanie
authors.initials: S
authors.lastname: Surget
authors.forename: Valérie
authors.initials: V
authors.lastname: Trichet
authors.forename: Lisa
authors.initials: L
authors.lastname: Oliver
authors.forename: Catherine
authors.initials: C
authors.lastname: Pellat-Deceunynck
authors.forename: Martine
authors.initials: M
authors.lastname: Amiot
mesh_terms: 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*
chemical_list: 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