Serine 162, an Essential Residue for the Mitochondrial Localization, Stability and Anti-Apoptotic Function of Mcl-1

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 biologyMutationTransport proteinNuclear localization sequenceMolecular biologyMutantMyeloid Cell Leukemia Sequence 1 ProteinSubcellular localizationBiologyMitochondrionPhosphorylation

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.

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