作者: Luke W Thomas , Connie Lam , Richard E Clark , Michael RH White , David G Spiller
DOI: 10.1371/JOURNAL.PONE.0045088
关键词: Cell biology 、 Mutation 、 Transport protein 、 Nuclear localization sequence 、 Molecular biology 、 Mutant 、 Myeloid Cell Leukemia Sequence 1 Protein 、 Subcellular localization 、 Biology 、 Mitochondrion 、 Phosphorylation
摘要: Mcl-1 is an anti-apoptotic member of the Bcl-2 family that plays a key role in normal development, but also pathologies such as cancer. It has some unusual properties compared to other members family, and its expression function are dynamically regulated by variety post-transcriptional post-translational processes. Of note, protein very short half life, stability may be reversible phosphorylation. There evidence suggest it localized different subcellular compartments. The aim this work was determine whether residues within PEST region undergo phosphorylation, regulate distribution. We show EGFP:Mcl-1 localizes mainly mitochondria HeLa cells, with additional cytoplasmic nuclear localization. mutations, S64A, S64E, S121A, S159A, T163A T163E did not significantly affect localization Mcl-1. However, mutation Ser162 phospho-null residue, Alanine resulted essentially localization, no mitochondrial This mutant protein, S162A, showed decreased ability protect against Bak-induced apoptosis. These data identify new molecular determinant function, important for understanding disease.