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Review
. 2022 Jun;289(11):3072-3085.
doi: 10.1111/febs.16029. Epub 2021 Jun 13.

Protein phosphatase 1: life-course regulation by SDS22 and Inhibitor-3

Xinyu Cao  1 , Sarah Lemaire  1 , Mathieu Bollen  1
Affiliations
Free article
Review

Protein phosphatase 1: life-course regulation by SDS22 and Inhibitor-3

Xinyu Cao et al. FEBS J. 2022 Jun.
Free article

Abstract

Protein phosphatase 1 (PP1) is expressed in all eukaryotic cells and catalyzes a sizable fraction of protein Ser/Thr dephosphorylation events. It is tightly regulated in space and time through association with a wide array of regulatory interactors of protein phosphatase one (RIPPOs). Suppressor-of-Dis2-number 2 (SDS22) and Inhibitor-3 (I3), which form a ternary complex with PP1, are the first two evolved and most widely expressed RIPPOs. Their deletion causes mitotic-arrest phenotypes and is lethal in some organisms. The role of SDS22 and I3 in PP1 regulation has been a mystery for decades as they were independently identified as both activators and inhibitors of PP1. This conundrum has largely been solved by recent reports showing that SDS22 and I3 control multiple steps of the life course of PP1. Indeed, they contribute to (a) the stabilization and activation of newly translated PP1, (b) the translocation of PP1 to the nucleus, and (c) the storage of PP1 as a reserve for holoenzyme assembly. Preliminary evidence suggests that SDS22 and I3 may also function as scavengers of released or aged PP1 for re-use in holoenzyme assembly or proteolytical degradation, respectively. Hence, SDS22 and I3 are emerging as master regulators of the life course of PP1.

Keywords: Cdc48/p97; Inhibitor-3; SDS22; biogenesis; life course; mitosis; protein phosphatase 1.

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References

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