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Cells 2014, 3(2), 418-437; doi:10.3390/cells3020418
Review

Mcl-1 Ubiquitination: Unique Regulation of an Essential Survival Protein

1,2,3
, 1,2,3
 and 1,2,3,*
Received: 13 March 2014; in revised form: 16 April 2014 / Accepted: 29 April 2014 / Published: 8 May 2014
(This article belongs to the Special Issue Protein Ubiquitination)
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Abstract: Mcl-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.
Keywords: Mcl-1; ubiquitin; proteasome; apoptosis; phosphorylation; E3 ubiquitin-ligase; deubiquitinase Mcl-1; ubiquitin; proteasome; apoptosis; phosphorylation; E3 ubiquitin-ligase; deubiquitinase
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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MDPI and ACS Style

Mojsa, B.; Lassot, I.; Desagher, S. Mcl-1 Ubiquitination: Unique Regulation of an Essential Survival Protein. Cells 2014, 3, 418-437.

AMA Style

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.


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