The study of the determinants controlling Arpp19 phosphatase-inhibitory activity reveals a new Arpp19/PP2A-B55 feedback loop

Jean Claude Labbe Sr., Suzanne Vigneron, Francisca Mechali, Perle Robert, Cindy Genoud, Perrine Goguet-Rubio, Philippe Barthe, Gilles Labesse, Martin Cohen-Gonsaud, Anna Castro, Thierry Lorca

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Received Date: 6th April 20

Arpp19 is a potent inhibitor of PP2A-B55 that regulates this phosphatase to ensure the stable phosphorylation of mitotic/meiotic substrates. At G2-M, Arpp19 is phosphorylated by Greatwall on S67. This phosphorylated Arpp19 form displays a high affinity to PP2A-B55 and a slow dephosphorylation rate, acting as an “unfair” competitor of PP2A-B55 substrates. The molecular determinants conferring slow dephosphorylation kinetics to S67 are unknown. PKA also phosphorylates Arpp19. This phosphorylation performed on S109 is essential to maintain prophase I-arrest in Xenopus oocytes although the underlying signaling mechanism is elusive. Here, we characterized the molecular determinants conferring slow dephosphorylation to S67 and controlling PP2A-B55 inhibitory activity of Arpp19. Moreover, we showed that phospho-S109 restricts S67 phosphorylation by increasing its catalysis by PP2A-B55. Finally, we discovered a double feed-back loop between these two phospho-sites which is essential to coordinate the temporal pattern of Arpp19-dependent PP2A-B55 inhibition and Cyclin B/Cdk1 activation during cell division.

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This is an abstract of a preprint hosted on an independent third party site. It has not been peer reviewed but is currently under consideration at Nature Communications.

Nature Communications

Nature Research, Springer Nature