Mcl-1 Ubiquitination: Unique Regulation of an Essential Survival Protein
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...
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| Format: | Article |
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MDPI AG
2014-05-01
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| Series: | Cells |
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| Online Access: | http://www.mdpi.com/2073-4409/3/2/418 |
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| author | Barbara Mojsa Iréna Lassot Solange Desagher |
| author_facet | Barbara Mojsa Iréna Lassot Solange Desagher |
| author_sort | Barbara Mojsa |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-12T11:00:10Z |
| format | Article |
| id | doaj.art-09c0e5b74a3147178c3b226feea88a56 |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-12T11:00:10Z |
| publishDate | 2014-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-09c0e5b74a3147178c3b226feea88a562023-09-02T05:44:54ZengMDPI AGCells2073-44092014-05-013241843710.3390/cells3020418cells3020418Mcl-1 Ubiquitination: Unique Regulation of an Essential Survival ProteinBarbara Mojsa0Iréna Lassot1Solange Desagher2Institut de Génétique Moléculaire de Montpellier UMR 5535 CNRS, 1919 route de Mende, 34293 Montpellier cedex 5, FranceInstitut de Génétique Moléculaire de Montpellier UMR 5535 CNRS, 1919 route de Mende, 34293 Montpellier cedex 5, FranceInstitut de Génétique Moléculaire de Montpellier UMR 5535 CNRS, 1919 route de Mende, 34293 Montpellier cedex 5, FranceMcl-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.http://www.mdpi.com/2073-4409/3/2/418Mcl-1ubiquitinproteasomeapoptosisphosphorylationE3 ubiquitin-ligasedeubiquitinase |
| spellingShingle | Barbara Mojsa Iréna Lassot Solange Desagher Mcl-1 Ubiquitination: Unique Regulation of an Essential Survival Protein Cells Mcl-1 ubiquitin proteasome apoptosis phosphorylation E3 ubiquitin-ligase deubiquitinase |
| title | Mcl-1 Ubiquitination: Unique Regulation of an Essential Survival Protein |
| title_full | Mcl-1 Ubiquitination: Unique Regulation of an Essential Survival Protein |
| title_fullStr | Mcl-1 Ubiquitination: Unique Regulation of an Essential Survival Protein |
| title_full_unstemmed | Mcl-1 Ubiquitination: Unique Regulation of an Essential Survival Protein |
| title_short | Mcl-1 Ubiquitination: Unique Regulation of an Essential Survival Protein |
| title_sort | mcl 1 ubiquitination unique regulation of an essential survival protein |
| topic | Mcl-1 ubiquitin proteasome apoptosis phosphorylation E3 ubiquitin-ligase deubiquitinase |
| url | http://www.mdpi.com/2073-4409/3/2/418 |
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