RT Journal Article
SR Electronic
T1 The study of the determinants controlling Arpp19 phosphatase-inhibitory activity reveals a new Arpp19/PP2A-B55 feedback loop
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2020.05.11.087890
DO 10.1101/2020.05.11.087890
A1 Jean Claude Labbé
A1 Suzanne Vigneron
A1 Francisca Méchali
A1 Perle Robert
A1 Cindy Genoud
A1 Perrine Goguet-Rubio
A1 Phillipe Barthe
A1 Gilles Labesse
A1 Martin Cohen-Gonsaud
A1 Anna Castro
A1 Thierry Lorca
YR 2020
UL http://biorxiv.org/content/early/2020/05/12/2020.05.11.087890.abstract
AB 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.Competing Interest StatementThe authors have declared no competing interest.