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

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Retinal degeneration depends on Bmi1 function and reactivation of cell cycle proteins. / Zencak, Dusan; Schouwey, Karine; Chen, Danian; Ekström, Per; Tanger, Ellen; Bremner, Rod; van Lohuizen, Maarten; Arsenijevic, Yvan.

In: Proceedings of the National Academy of Sciences, Vol. 110, No. 7, 2013, p. E593-E601.

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Zencak, D, Schouwey, K, Chen, D, Ekström, P, Tanger, E, Bremner, R, van Lohuizen, M & Arsenijevic, Y 2013, 'Retinal degeneration depends on Bmi1 function and reactivation of cell cycle proteins', Proceedings of the National Academy of Sciences, vol. 110, no. 7, pp. E593-E601. https://doi.org/10.1073/pnas.1108297110

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Zencak, Dusan ; Schouwey, Karine ; Chen, Danian ; Ekström, Per ; Tanger, Ellen ; Bremner, Rod ; van Lohuizen, Maarten ; Arsenijevic, Yvan. / Retinal degeneration depends on Bmi1 function and reactivation of cell cycle proteins. In: Proceedings of the National Academy of Sciences. 2013 ; Vol. 110, No. 7. pp. E593-E601.

RIS

TY - JOUR

T1 - Retinal degeneration depends on Bmi1 function and reactivation of cell cycle proteins

AU - Zencak, Dusan

AU - Schouwey, Karine

AU - Chen, Danian

AU - Ekström, Per

AU - Tanger, Ellen

AU - Bremner, Rod

AU - van Lohuizen, Maarten

AU - Arsenijevic, Yvan

PY - 2013

Y1 - 2013

N2 - 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.

AB - 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.

KW - blindness

KW - neurodegeneration

KW - polycomb

U2 - 10.1073/pnas.1108297110

DO - 10.1073/pnas.1108297110

M3 - Article

VL - 110

SP - E593-E601

JO - Proceedings of the National Academy of Sciences

JF - Proceedings of the National Academy of Sciences

SN - 1091-6490

IS - 7

ER -