The MAL Protein, an Integral Component of Specialized Membranes, in Normal Cells and Cancer
The <i>MAL</i> gene encodes a 17-kDa protein containing four putative transmembrane segments whose expression is restricted to human T cells, polarized epithelial cells and myelin-forming cells. The MAL protein has two unusual biochemical features. First, it has lipid-like properties tha...
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-04-01
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| Series: | Cells |
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| Online Access: | https://www.mdpi.com/2073-4409/10/5/1065 |
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| author | Armando Rubio-Ramos Leticia Labat-de-Hoz Isabel Correas Miguel A. Alonso |
| author_facet | Armando Rubio-Ramos Leticia Labat-de-Hoz Isabel Correas Miguel A. Alonso |
| author_sort | Armando Rubio-Ramos |
| collection | DOAJ |
| description | The <i>MAL</i> gene encodes a 17-kDa protein containing four putative transmembrane segments whose expression is restricted to human T cells, polarized epithelial cells and myelin-forming cells. The MAL protein has two unusual biochemical features. First, it has lipid-like properties that qualify it as a member of the group of proteolipid proteins. Second, it partitions selectively into detergent-insoluble membranes, which are known to be enriched in condensed cell membranes, consistent with MAL being distributed in highly ordered membranes in the cell. Since its original description more than thirty years ago, a large body of evidence has accumulated supporting a role of MAL in specialized membranes in all the cell types in which it is expressed. Here, we review the structure, expression and biochemical characteristics of MAL, and discuss the association of MAL with raft membranes and the function of MAL in polarized epithelial cells, T lymphocytes, and myelin-forming cells. The evidence that MAL is a putative receptor of the epsilon toxin of <i>Clostridium perfringens</i>, the expression of MAL in lymphomas, the hypermethylation of the <i>MAL</i> gene and subsequent loss of MAL expression in carcinomas are also presented. We propose a model of MAL as the organizer of specialized condensed membranes to make them functional, discuss the role of MAL as a tumor suppressor in carcinomas, consider its potential use as a cancer biomarker, and summarize the directions for future research. |
| first_indexed | 2024-03-10T11:48:39Z |
| format | Article |
| id | doaj.art-e4b6c497693d4be2992ec6c341743688 |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-10T11:48:39Z |
| publishDate | 2021-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-e4b6c497693d4be2992ec6c3417436882023-11-21T17:56:57ZengMDPI AGCells2073-44092021-04-01105106510.3390/cells10051065The MAL Protein, an Integral Component of Specialized Membranes, in Normal Cells and CancerArmando Rubio-Ramos0Leticia Labat-de-Hoz1Isabel Correas2Miguel A. Alonso3Centro de Biología Molecular “Severo Ochoa”, Consejo Superior de Investigaciones Científicas and Universidad Autónoma de Madrid, 28049 Madrid, SpainCentro de Biología Molecular “Severo Ochoa”, Consejo Superior de Investigaciones Científicas and Universidad Autónoma de Madrid, 28049 Madrid, SpainCentro de Biología Molecular “Severo Ochoa”, Consejo Superior de Investigaciones Científicas and Universidad Autónoma de Madrid, 28049 Madrid, SpainCentro de Biología Molecular “Severo Ochoa”, Consejo Superior de Investigaciones Científicas and Universidad Autónoma de Madrid, 28049 Madrid, SpainThe <i>MAL</i> gene encodes a 17-kDa protein containing four putative transmembrane segments whose expression is restricted to human T cells, polarized epithelial cells and myelin-forming cells. The MAL protein has two unusual biochemical features. First, it has lipid-like properties that qualify it as a member of the group of proteolipid proteins. Second, it partitions selectively into detergent-insoluble membranes, which are known to be enriched in condensed cell membranes, consistent with MAL being distributed in highly ordered membranes in the cell. Since its original description more than thirty years ago, a large body of evidence has accumulated supporting a role of MAL in specialized membranes in all the cell types in which it is expressed. Here, we review the structure, expression and biochemical characteristics of MAL, and discuss the association of MAL with raft membranes and the function of MAL in polarized epithelial cells, T lymphocytes, and myelin-forming cells. The evidence that MAL is a putative receptor of the epsilon toxin of <i>Clostridium perfringens</i>, the expression of MAL in lymphomas, the hypermethylation of the <i>MAL</i> gene and subsequent loss of MAL expression in carcinomas are also presented. We propose a model of MAL as the organizer of specialized condensed membranes to make them functional, discuss the role of MAL as a tumor suppressor in carcinomas, consider its potential use as a cancer biomarker, and summarize the directions for future research.https://www.mdpi.com/2073-4409/10/5/1065condensed membranesmembrane traffickingtoxinsepithelial cellsT cellsmyelin-forming cells |
| spellingShingle | Armando Rubio-Ramos Leticia Labat-de-Hoz Isabel Correas Miguel A. Alonso The MAL Protein, an Integral Component of Specialized Membranes, in Normal Cells and Cancer Cells condensed membranes membrane trafficking toxins epithelial cells T cells myelin-forming cells |
| title | The MAL Protein, an Integral Component of Specialized Membranes, in Normal Cells and Cancer |
| title_full | The MAL Protein, an Integral Component of Specialized Membranes, in Normal Cells and Cancer |
| title_fullStr | The MAL Protein, an Integral Component of Specialized Membranes, in Normal Cells and Cancer |
| title_full_unstemmed | The MAL Protein, an Integral Component of Specialized Membranes, in Normal Cells and Cancer |
| title_short | The MAL Protein, an Integral Component of Specialized Membranes, in Normal Cells and Cancer |
| title_sort | mal protein an integral component of specialized membranes in normal cells and cancer |
| topic | condensed membranes membrane trafficking toxins epithelial cells T cells myelin-forming cells |
| url | https://www.mdpi.com/2073-4409/10/5/1065 |
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