Regulation of cell proliferation in the retinal pigment epithelium: Differential regulation of the death‐associated protein like‐1 DAPL1 by alternative MITF splice forms
Summary Vertebrate eye development and homoeostasis critically depend on the regulation of proliferation of cells forming the retinal pigment epithelium (RPE). Previous results indicated that the death‐associated protein like‐1 DAPL1 cell autonomously suppresses RPE proliferation in vivo and in vitr...
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| Published in | Pigment cell and melanoma research Vol. 31; no. 3; pp. 411 - 422 |
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| Main Authors | , , , , , , , , |
| Format | Journal Article |
| Language | English |
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01.05.2018
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| Abstract | Summary
Vertebrate eye development and homoeostasis critically depend on the regulation of proliferation of cells forming the retinal pigment epithelium (RPE). Previous results indicated that the death‐associated protein like‐1 DAPL1 cell autonomously suppresses RPE proliferation in vivo and in vitro. Here, we show in human RPE cell lines that the pigment cell transcription factor MITF regulates RPE cell proliferation by upregulating DAPL1 expression. DAPL1 regulation by MITF is, however, mediated predominantly by (−) MITF, one of two alternative splice isoforms of MITF that lacks six residues located upstream of the DNA‐binding basic domain. Furthermore, we find that the regulation of DAPL1 by MITF is indirect in that (−) MITF stimulates the transcription of Musashi homolog‐2 (MSI2), which negatively regulates the processing of the anti‐DAPL1 microRNA miR‐7. Our results provide molecular insights into the regulation of RPE cell proliferation and quiescence and may help us understand the mechanisms of normal RPE maintenance and of eye diseases associated with either RPE hyperproliferation or the lack of regenerative proliferation. |
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| AbstractList | Vertebrate eye development and homoeostasis critically depend on the regulation of proliferation of cells forming the retinal pigment epithelium (RPE). Previous results indicated that the death‐associated protein like‐1 DAPL1 cell autonomously suppresses RPE proliferation in vivo and in vitro. Here, we show in human RPE cell lines that the pigment cell transcription factor MITF regulates RPE cell proliferation by upregulating DAPL1 expression. DAPL1 regulation by MITF is, however, mediated predominantly by (−) MITF, one of two alternative splice isoforms of MITF that lacks six residues located upstream of the DNA‐binding basic domain. Furthermore, we find that the regulation of DAPL1 by MITF is indirect in that (−) MITF stimulates the transcription of Musashi homolog‐2 (MSI2), which negatively regulates the processing of the anti‐DAPL1 microRNA miR‐7. Our results provide molecular insights into the regulation of RPE cell proliferation and quiescence and may help us understand the mechanisms of normal RPE maintenance and of eye diseases associated with either RPE hyperproliferation or the lack of regenerative proliferation. Summary Vertebrate eye development and homoeostasis critically depend on the regulation of proliferation of cells forming the retinal pigment epithelium (RPE). Previous results indicated that the death‐associated protein like‐1 DAPL1 cell autonomously suppresses RPE proliferation in vivo and in vitro. Here, we show in human RPE cell lines that the pigment cell transcription factor MITF regulates RPE cell proliferation by upregulating DAPL1 expression. DAPL1 regulation by MITF is, however, mediated predominantly by (−) MITF, one of two alternative splice isoforms of MITF that lacks six residues located upstream of the DNA‐binding basic domain. Furthermore, we find that the regulation of DAPL1 by MITF is indirect in that (−) MITF stimulates the transcription of Musashi homolog‐2 (MSI2), which negatively regulates the processing of the anti‐DAPL1 microRNA miR‐7. Our results provide molecular insights into the regulation of RPE cell proliferation and quiescence and may help us understand the mechanisms of normal RPE maintenance and of eye diseases associated with either RPE hyperproliferation or the lack of regenerative proliferation. Vertebrate eye development and homoeostasis critically depend on the regulation of proliferation of cells forming the retinal pigment epithelium (RPE). Previous results indicated that the death-associated protein like-1 DAPL1 cell autonomously suppresses RPE proliferation in vivo and in vitro. Here, we show in human RPE cell lines that the pigment cell transcription factor MITF regulates RPE cell proliferation by upregulating DAPL1 expression. DAPL1 regulation by MITF is, however, mediated predominantly by (-) MITF, one of two alternative splice isoforms of MITF that lacks six residues located upstream of the DNA-binding basic domain. Furthermore, we find that the regulation of DAPL1 by MITF is indirect in that (-) MITF stimulates the transcription of Musashi homolog-2 (MSI2), which negatively regulates the processing of the anti-DAPL1 microRNA miR-7. Our results provide molecular insights into the regulation of RPE cell proliferation and quiescence and may help us understand the mechanisms of normal RPE maintenance and of eye diseases associated with either RPE hyperproliferation or the lack of regenerative proliferation. |
| Author | Hua, Jiajia Li, Huirong Rao, Chunbao Li, Fang Ma, Xiaoyin Zheng, Guoxiao Pan, Li Wang, Jing Hou, Ling |
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| Keywords | MITF pigment cell retinal pigment epithelium alternative splicing age-related macular degeneration |
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Vertebrate eye development and homoeostasis critically depend on the regulation of proliferation of cells forming the retinal pigment epithelium (RPE).... Vertebrate eye development and homoeostasis critically depend on the regulation of proliferation of cells forming the retinal pigment epithelium (RPE).... |
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| SubjectTerms | age‐related macular degeneration Alternative splicing Cell growth Cell lines Cell proliferation Deoxyribonucleic acid DNA Epithelium Eye diseases Homology Isoforms Kinases miRNA MITF pigment cell Retina Retinal pigment epithelium Ribonucleic acid RNA |
| Title | Regulation of cell proliferation in the retinal pigment epithelium: Differential regulation of the death‐associated protein like‐1 DAPL1 by alternative MITF splice forms |
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