Abstract
pRb is dephosphorylated at mitotic exit by the type 1 serine/threonine protein phosphatases (PP1). Here we demonstrate for the first time that mitotic pRb dephosphorylation is a sequential, temporally-regulated event. We also provide evidence that the three mammalian isoforms of PP1, α, γ-1, and δ, differ in their respective preferences for site-specific pRb dephosphorylation and that the mitotic and G1 PP1-isoform counterparts exhibit differential activities towards mitotic pRb. Finally, the physiological relevance of the striking contrast between the patterns of Thr821 and Thr826 dephosphorylation, sites known to be important for disrupting binding of LXCXE-containing proteins to pRb, is addressed.
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Acknowledgements
This work was supported by Research Project Grant # 98-108 from the American Cancer Society, The Sally Edelman and Harry Gardner Cancer Research Foundation (awarded to JW Ludlow), and Cancer Center Core Grant CA11198.
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Rubin, E., Mittnacht, S., Villa-Moruzzi, E. et al. Site-specific and temporally-regulated retinoblastoma protein dephosphorylation by protein phosphatase type 1. Oncogene 20, 3776–3785 (2001). https://doi.org/10.1038/sj.onc.1204518
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DOI: https://doi.org/10.1038/sj.onc.1204518
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