Retinal degeneration depends on Bmi1 function and reactivation of cell cycle proteins

The epigenetic regulator Bmi1 controls proliferation in many organs. Reexpression of cell cycle proteins such as cyclin-dependent kinases (CDKs) is a hallmark of neuronal apoptosis in neurodegenerative diseases. Here we address the potential role of Bmi1 as a key regulator of cell cycle proteins dur...

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Vydáno v:Proceedings of the National Academy of Sciences - PNAS Ročník 110; číslo 7; s. E593
Hlavní autoři: Zencak, Dusan, Schouwey, Karine, Chen, Danian, Ekström, Per, Tanger, Ellen, Bremner, Rod, van Lohuizen, Maarten, Arsenijevic, Yvan
Médium: Journal Article
Jazyk:angličtina
Vydáno: United States 12.02.2013
Témata:
Analysis of Variance
Animals
Apoptosis - physiology
Cell Cycle Proteins - metabolism
E2F1 Transcription Factor - metabolism
Epigenesis, Genetic - genetics
Epigenesis, Genetic - physiology
Gene Expression Regulation - genetics
Gene Expression Regulation - physiology
Histological Techniques
Mice
Mice, Knockout
Microscopy, Fluorescence
Polycomb Repressive Complex 1 - genetics
Polycomb Repressive Complex 1 - metabolism
Proto-Oncogene Proteins - genetics
Proto-Oncogene Proteins - metabolism
Retinal Degeneration - metabolism
ISSN:1091-6490, 1091-6490
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Popis
Shrnutí:The epigenetic regulator Bmi1 controls proliferation in many organs. Reexpression of cell cycle proteins such as cyclin-dependent kinases (CDKs) is a hallmark of neuronal apoptosis in neurodegenerative diseases. Here we address the potential role of Bmi1 as a key regulator of cell cycle proteins during neuronal apoptosis. We show that several cell cycle proteins are expressed in different models of retinal degeneration and required in the Rd1 photoreceptor death process. Deleting E2f1, a downstream target of CDKs, provided temporary protection in Rd1 mice. Most importantly, genetic ablation of Bmi1 provided extensive photoreceptor survival and improvement of retinal function in Rd1 mice, mediated by a decrease in cell cycle markers and regulators independent of p16(Ink4a) and p19(Arf). These data reveal that Bmi1 controls the cell cycle-related death process, highlighting this pathway as a promising therapeutic target for neuroprotection in retinal dystrophies.
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ISSN:1091-6490
1091-6490
DOI:10.1073/pnas.1108297110