Mcl-1 ubiquitination: unique regulation of an essential survival protein

摘要: Mcl-1 is an anti-apoptotic protein of the Bcl-2 family that essential for survival multiple cell lineages and highly amplified in human cancer. Under physiological conditions, expression tightly regulated at levels, involving transcriptional, post-transcriptional post-translational processes. Ubiquitination Mcl-1, targets it proteasomal degradation, allows rapid elimination triggering death, response to various cellular events. In last decade, a number studies have elucidated different pathways controlling ubiquitination degradation. Four E3 ubiquitin-ligases (e.g., Mule, SCFβ-TrCP, SCFFbw7 Trim17) one deubiquitinase USP9X), respectively mediate oppose ubiquitination, been formerly identified. The interaction between Mule can be modulated by other proteins, while recognition influenced phosphorylation specific residues Mcl-1. kinases are involved regulation stability vary depending on context, highlighting complexity pivotal role regulation. this review, we attempt recapitulate progress understanding ubiquitin-proteasome system.