Phosphatases in Mitosis: Roles and Regulation

Abstract

Mitosis requires extensive rearrangement of cellular architecture and of subcellular structures so that replicated chromosomes can bind correctly to spindle microtubules and segregate towards opposite poles. This process originates two new daughter nuclei with equal genetic content and relies on highly-dynamic and tightly regulated phosphorylation of numerous cell cycle proteins. A burst in protein phosphorylation orchestrated by several conserved kinases occurs as cells go into and progress through mitosis. The opposing dephosphorylation events are catalyzed by a small set of protein phosphatases, whose importance for the accuracy of mitosis is becoming increasingly appreciated. This review will focus on the established and emerging roles of mitotic phosphatases, describe their structural and biochemical properties, and discuss recent advances in understanding the regulation of phosphatase activity and function.

Polo regulates Spindly to prevent premature stabilization of kinetochore–microtubule attachments

“…PP2A‐B56 phosphatase may have a role in this process, since impairing its association with BubR1 was recently shown to dramatically increase the frequency of laterally attached KTs in human cells (Shrestha et al , ). However, because BubR1‐PP2A‐B56 is already present at high levels on early mitotic KTs, we reason that additional mechanisms must operate to prevent premature end‐on conversion (Moura & Conde, ). It is plausible that the switch is determined by the levels of cyclin A, which have been shown to function as a timer in prometaphase to destabilize attachments and facilitate error correction (Kabeche & Compton, ).…”

The M-phase regulatory phosphatase PP2A-B55δ opposes protein kinase A on Arpp19 to initiate meiotic division

“…Each of the four B subfamilies comprises several isoforms with very closely related sequences, no discernible differences in their substrate binding pockets and substantial substrate specificity overlap 44 . In the present study, our biochemical isolation procedures identify B55δ as being associated with PP2A-A/C that dephosphorylates Arpp19 at S109.…”

Mitotic ER exit site dissociation and reassembly is regulated by TANGO1 phosphorylation status

“…In terms of regulatory activity, PP1 normally assembles to holoenzyme complexes with regulatory subunits. To date, hundreds of holoenzymes have been identified (Moura and Conde, 2019; Nilsson, 2019). Each holoenzyme shows distinct localization and different substrate binding properties according to the regulatory subunit.…”