Physiological Functions of Mcl-1: Insights From Genetic Mouse Models
The ability to regulate the survival and death of a cell is paramount throughout the lifespan of a multicellular organism. Apoptosis, a main physiological form of programmed cell death, is regulated by the Bcl-2 family proteins that are either pro-apoptotic or pro-survival. The in vivo functions of...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2021-07-01
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| Series: | Frontiers in Cell and Developmental Biology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fcell.2021.704547/full |
| _version_ | 1819071071400230912 |
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| author | Hui San Chin Nai Yang Fu Nai Yang Fu |
| author_facet | Hui San Chin Nai Yang Fu Nai Yang Fu |
| author_sort | Hui San Chin |
| collection | DOAJ |
| description | The ability to regulate the survival and death of a cell is paramount throughout the lifespan of a multicellular organism. Apoptosis, a main physiological form of programmed cell death, is regulated by the Bcl-2 family proteins that are either pro-apoptotic or pro-survival. The in vivo functions of distinct Bcl-2 family members are largely unmasked by genetically engineered murine models. Mcl-1 is one of the two Bcl-2 like pro-survival genes whose germline deletion causes embryonic lethality in mice. Its requisite for the survival of a broad range of cell types has been further unraveled by using conditional and inducible deletion murine model systems in different tissues or cell lineages and at distinct developmental stages. Moreover, genetic mouse cancer models have also demonstrated that Mcl-1 is essential for the survival of multiple tumor types. The MCL-1 locus is commonly amplified across various cancer types in humans. Small molecule inhibitors with high affinity and specificity to human MCL-1 have been developed and explored for the treatment of certain cancers. To facilitate the pre-clinical studies of MCL-1 in cancer and other diseases, transgenic mouse models over-expressing human MCL-1 as well as humanized MCL-1 mouse models have been recently engineered. This review discusses the current advances in understanding the physiological roles of Mcl-1 based on studies using genetic murine models and its critical implications in pathology and treatment of human diseases. |
| first_indexed | 2024-12-21T17:16:00Z |
| format | Article |
| id | doaj.art-a3fa7f431ce64431ad5d366d53a859b3 |
| institution | Directory Open Access Journal |
| issn | 2296-634X |
| language | English |
| last_indexed | 2024-12-21T17:16:00Z |
| publishDate | 2021-07-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cell and Developmental Biology |
| spelling | doaj.art-a3fa7f431ce64431ad5d366d53a859b32022-12-21T18:56:18ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2021-07-01910.3389/fcell.2021.704547704547Physiological Functions of Mcl-1: Insights From Genetic Mouse ModelsHui San Chin0Nai Yang Fu1Nai Yang Fu2Programme in Cancer and Stem Cell Biology, Duke-NUS Medical School, Singapore, SingaporeProgramme in Cancer and Stem Cell Biology, Duke-NUS Medical School, Singapore, SingaporeDepartment of Physiology, National University of Singapore, Singapore, SingaporeThe ability to regulate the survival and death of a cell is paramount throughout the lifespan of a multicellular organism. Apoptosis, a main physiological form of programmed cell death, is regulated by the Bcl-2 family proteins that are either pro-apoptotic or pro-survival. The in vivo functions of distinct Bcl-2 family members are largely unmasked by genetically engineered murine models. Mcl-1 is one of the two Bcl-2 like pro-survival genes whose germline deletion causes embryonic lethality in mice. Its requisite for the survival of a broad range of cell types has been further unraveled by using conditional and inducible deletion murine model systems in different tissues or cell lineages and at distinct developmental stages. Moreover, genetic mouse cancer models have also demonstrated that Mcl-1 is essential for the survival of multiple tumor types. The MCL-1 locus is commonly amplified across various cancer types in humans. Small molecule inhibitors with high affinity and specificity to human MCL-1 have been developed and explored for the treatment of certain cancers. To facilitate the pre-clinical studies of MCL-1 in cancer and other diseases, transgenic mouse models over-expressing human MCL-1 as well as humanized MCL-1 mouse models have been recently engineered. This review discusses the current advances in understanding the physiological roles of Mcl-1 based on studies using genetic murine models and its critical implications in pathology and treatment of human diseases.https://www.frontiersin.org/articles/10.3389/fcell.2021.704547/fullBcl-2Mcl-1apoptosiscell deathmitochondriagenetic mouse model |
| spellingShingle | Hui San Chin Nai Yang Fu Nai Yang Fu Physiological Functions of Mcl-1: Insights From Genetic Mouse Models Frontiers in Cell and Developmental Biology Bcl-2 Mcl-1 apoptosis cell death mitochondria genetic mouse model |
| title | Physiological Functions of Mcl-1: Insights From Genetic Mouse Models |
| title_full | Physiological Functions of Mcl-1: Insights From Genetic Mouse Models |
| title_fullStr | Physiological Functions of Mcl-1: Insights From Genetic Mouse Models |
| title_full_unstemmed | Physiological Functions of Mcl-1: Insights From Genetic Mouse Models |
| title_short | Physiological Functions of Mcl-1: Insights From Genetic Mouse Models |
| title_sort | physiological functions of mcl 1 insights from genetic mouse models |
| topic | Bcl-2 Mcl-1 apoptosis cell death mitochondria genetic mouse model |
| url | https://www.frontiersin.org/articles/10.3389/fcell.2021.704547/full |
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