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Mcl-1 Ubiquitination: Unique Regulation of an Essential Survival Protein
AbstractMcl-1 is an anti-apoptotic protein of the Bcl-2 family that is essential for the survival of multiple cell lineages and that is highly amplified in human cancer. Under physiological conditions, Mcl-1 expression is tightly regulated at multiple levels, involving transcriptional, post-transcriptional and post-translational processes. Ubiquitination of Mcl-1, that targets it for proteasomal degradation, allows for rapid elimination of the protein and triggering of cell death, in response to various cellular events. In the last decade, a number of studies have elucidated different pathways controlling Mcl-1 ubiquitination and degradation. Four different E3 ubiquitin-ligases (e.g., Mule, SCFβ-TrCP, SCFFbw7 and Trim17) and one deubiquitinase (e.g., USP9X), that respectively mediate and oppose Mcl-1 ubiquitination, have been formerly identified. The interaction between Mule and Mcl-1 can be modulated by other Bcl-2 family proteins, while recognition of Mcl-1 by the other E3 ubiquitin-ligases and deubiquitinase is influenced by phosphorylation of specific residues in Mcl-1. The protein kinases and E3 ubiquitin-ligases that are involved in the regulation of Mcl-1 stability vary depending on the cellular context, highlighting the complexity and pivotal role of Mcl-1 regulation. In this review, we attempt to recapitulate progress in understanding Mcl-1 regulation by the ubiquitin-proteasome system.
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Mojsa, B.; Lassot, I.; Desagher, S. Mcl-1 Ubiquitination: Unique Regulation of an Essential Survival Protein. Cells 2014, 3, 418-437.View more citation formats
Mojsa B, Lassot I, Desagher S. Mcl-1 Ubiquitination: Unique Regulation of an Essential Survival Protein. Cells. 2014; 3(2):418-437.Chicago/Turabian Style
Mojsa, Barbara; Lassot, Iréna; Desagher, Solange. 2014. "Mcl-1 Ubiquitination: Unique Regulation of an Essential Survival Protein." Cells 3, no. 2: 418-437.