scholarly journals Cyclin B–Cdk1 inhibits protein phosphatase PP2A-B55 via a Greatwall kinase–independent mechanism

2014 ◽  
Vol 204 (6) ◽  
pp. 881-889 ◽  
Author(s):  
Eiichi Okumura ◽  
Atsushi Morita ◽  
Mizuho Wakai ◽  
Satoru Mochida ◽  
Masatoshi Hara ◽  
...  
Keyword(s):  
Protein Phosphatase ◽  
Cyclin B ◽  
Mitotic Progression ◽  
Independent Mechanism ◽  
M Phase ◽  
Dependent Inhibition ◽  
Phosphatase 2A ◽  
Initial Activation ◽  
Greatwall Kinase ◽  
Different Levels

Entry into M phase is governed by cyclin B–Cdk1, which undergoes both an initial activation and subsequent autoregulatory activation. A key part of the autoregulatory activation is the cyclin B–Cdk1–dependent inhibition of the protein phosphatase 2A (PP2A)–B55, which antagonizes cyclin B–Cdk1. Greatwall kinase (Gwl) is believed to be essential for the autoregulatory activation because Gwl is activated downstream of cyclin B–Cdk1 to phosphorylate and activate α-endosulfine (Ensa)/Arpp19, an inhibitor of PP2A-B55. However, cyclin B–Cdk1 becomes fully activated in some conditions lacking Gwl, yet how this is accomplished remains unclear. We show here that cyclin B–Cdk1 can directly phosphorylate Arpp19 on a different conserved site, resulting in inhibition of PP2A-B55. Importantly, this novel bypass is sufficient for cyclin B–Cdk1 autoregulatory activation. Gwl-dependent phosphorylation of Arpp19 is nonetheless necessary for downstream mitotic progression because chromosomes fail to segregate properly in the absence of Gwl. Such a biphasic regulation of Arpp19 results in different levels of PP2A-B55 inhibition and hence might govern its different cellular roles.

scholarly journals Cyclin A triggers Mitosis either via Greatwall or Cyclin B

2018 ◽  
Author(s):  
Nadia Hégarat ◽  
Adrijana Crncec ◽  
Maria F. Suarez Peredoa Rodri-guez ◽  
Fabio Echegaray Iturra ◽  
Yan Gu ◽  
...  
Keyword(s):  
Cyclin A ◽  
Cyclin B ◽  
Mitotic Progression ◽  
Nuclear Envelope Breakdown ◽  
Distinct Subset ◽  
Initial Activation ◽  
Greatwall Kinase ◽  
G2 Phase ◽  
Higher Eukaryotes ◽  
Complete Cell

AbstractTwo mitotic Cyclins, A and B, exist in higher eukaryotes, but their specialised functions in mitosis are poorly understood. Using degron tags we analyse how acute depletion of these proteins affects mitosis. Loss of Cyclin A in G2-phase prevents the initial activation of Cdk1. Cells lacking Cyclin B can enter mitosis and phosphorylate most mitotic proteins, because of parallel PP2A:B55 phos-phatase inactivation by Greatwall kinase. The final barrier to mitotic establishment corresponds to nuclear envelope breakdown that requires a decisive shift in the balance of Cdk1 and PP2A:B55 activity. Beyond this point Cyclin B/Cdk1 is essential to phosphorylate a distinct subset mitotic Cdk1 substrates that are essential to complete cell division. Our results identify how Cyclin A, B and Greatwall coordinate mitotic progression by increasing levels of Cdk1-dependent substrate phos-phorylation.

scholarly journals Transcriptional regulation mediated by H2A.Z via ANP32e-dependent inhibition of protein phosphatase 2A

2018 ◽  
Vol 1861 (5) ◽  
pp. 481-496 ◽  
Author(s):  
Hyewon Shin ◽  
Minzhen He ◽  
Zhi Yang ◽  
Yong Heui Jeon ◽  
Jessica Pfleger ◽  
...  
Keyword(s):  
Transcriptional Regulation ◽  
Protein Phosphatase ◽  
Protein Phosphatase 2A ◽  
Dependent Inhibition ◽  
Phosphatase 2A

scholarly journals Protein Phosphatase 2A (PP2A) Regulates EG5 to Control Mitotic Progression

2017 ◽  
Vol 7 (1) ◽  
Author(s):  
Yang Liu ◽  
Zhong Zhang ◽  
Hui Liang ◽  
Xuyang Zhao ◽  
Ling Liang ◽  
...  
Keyword(s):  
Protein Phosphatase ◽  
Protein Phosphatase 2A ◽  
Mitotic Progression ◽  
Phosphatase 2A

scholarly journals Inhibition of cdc2 activation by INH/PP2A.

1994 ◽  
Vol 5 (3) ◽  
pp. 323-338 ◽  
Author(s):  
T H Lee ◽  
C Turck ◽  
M W Kirschner
Keyword(s):  
Tyrosine Kinase ◽  
Protein Phosphatase ◽  
Tyrosine Phosphatase ◽  
Cyclin B ◽  
Reaction Pathways ◽  
Regulatory Subunit ◽  
Conventional Form ◽  
M Phase ◽  
Rate Limiting ◽  
Cdc2 Activity

INH, a type 2A protein phosphatase (PP2A), negatively regulates entry into M phase and the cyclin B-dependent activation of cdc2 in Xenopus extracts. INH appears to be central to the mechanism of the trigger for mitotic initiation, as it prevents the premature activation of cdc2. We first show that INH is a conventional form of PP2A with a B alpha regulatory subunit. We next explore the mechanism by which it inhibits cdc2 activation by examining the effect of purified PP2A on the reaction pathways controlling cdc2 activity. Our results suggest that although PP2A inhibits the switch in tyrosine kinase and tyrosine phosphatase activities accompanying mitosis, this switch is a consequence of the inhibition of some other rate-limiting event. In the preactivation phase, PP2A inhibits the pathway leading to T161 phosphorylation, suggesting that this activity may be one of the rate-limiting events for transition. However, our results also suggest that the accumulation of active cdc2/cyclin complexes during the lag is only one of the events required for triggering entry into mitosis.

Protein phosphatase 2A is required for mesalazine-dependent inhibition of Wnt/ -catenin pathway activity

2006 ◽  
Vol 27 (12) ◽  
pp. 2371-2382 ◽  
Author(s):  
C. L. Bos ◽  
S. H. Diks ◽  
J. C.H. Hardwick ◽  
K. V. Walburg ◽  
M. P. Peppelenbosch ◽  
...  
Keyword(s):  
Protein Phosphatase ◽  
Protein Phosphatase 2A ◽  
Pathway Activity ◽  
Dependent Inhibition ◽  
Phosphatase 2A

scholarly journals Regulation of Greatwall kinase during Xenopus oocyte maturation

2011 ◽  
Vol 22 (13) ◽  
pp. 2157-2164 ◽  
Author(s):  
Tomomi M. Yamamoto ◽  
Kristina Blake-Hodek ◽  
Byron C. Williams ◽  
Andrea L. Lewellyn ◽  
Michael L. Goldberg ◽  
...  
Keyword(s):  
Oocyte Maturation ◽  
Mammalian Cells ◽  
Xenopus Oocytes ◽  
Kinase Activity ◽  
Wild Type ◽  
M Phase ◽  
Phosphatase 2A ◽  
Greatwall Kinase ◽  
Related Proteins

Greatwall kinase has been identified as a key element in M phase initiation and maintenance in Drosophila, Xenopus oocytes/eggs, and mammalian cells. In M phase, Greatwall phosphorylates endosulfine and related proteins that bind to and inhibit protein phosphatase 2A/B55, the principal phosphatase for Cdk-phosphorylated substrates. We show that Greatwall binds active PP2A/B55 in G2 phase oocytes but dissociates from it when progesterone-treated oocytes reach M phase. This dissociation does not require Greatwall kinase activity or phosphorylation at T748 in the presumptive T loop of the kinase. A mutant K71M Greatwall, also known as Scant in Drosophila, induces M phase in the absence of progesterone when expressed in oocytes, despite its reduced stability and elevated degradation by the proteasome. M phase induction by Scant Greatwall requires protein synthesis but is not associated with altered binding or release of PP2A/B55 as compared to wild-type Greatwall. However, in vitro studies with Greatwall proteins purified from interphase cells indicate that Scant, but not wild-type Greatwall, has low but detectable activity against endosulfine. These results demonstrate progesterone-dependent regulation of the PP2A/B55–Greatwall interaction during oocyte maturation and suggest that the cognate Scant Greatwall mutation has sufficient constitutive kinase activity to promote M phase in Xenopus oocytes.

scholarly journals Suppression of Scant Identifies Endos as a Substrate of Greatwall Kinase and a Negative Regulator of Protein Phosphatase 2A in Mitosis

PLoS Genetics ◽  
2011 ◽  
Vol 7 (8) ◽  
pp. e1002225 ◽  
Author(s):  
Hélène Rangone ◽  
Eva Wegel ◽  
Melanie K. Gatt ◽  
Eirene Yeung ◽  
Alexander Flowers ◽  
...  
Keyword(s):  
Protein Phosphatase ◽  
Protein Phosphatase 2A ◽  
Negative Regulator ◽  
Phosphatase 2A ◽  
Greatwall Kinase

scholarly journals Regulation of the Cyclin B Degradation System by an Inhibitor of Mitotic Proteolysis

1998 ◽  
Vol 9 (7) ◽  
pp. 1817-1831 ◽  
Author(s):  
Elisabeth Vorlaufer ◽  
Jan-Michael Peters
Keyword(s):  
Okadaic Acid ◽  
Protein Phosphatase ◽  
Cyclin B ◽  
Protein Phosphatase 1 ◽  
Anaphase Promoting Complex ◽  
Egg Extracts ◽  
Mitotic Cyclin ◽  
Phosphatase 2A ◽  
Cytostatic Factor ◽  
Xenopus Egg Extracts

The initiation of anaphase and exit from mitosis depend on the anaphase-promoting complex (APC), which mediates the ubiquitin-dependent proteolysis of anaphase-inhibiting proteins and mitotic cyclins. We have analyzed whether protein phosphatases are required for mitotic APC activation. In Xenopus egg extracts APC activation occurs normally in the presence of protein phosphatase 1 inhibitors, suggesting that the anaphase defects caused by protein phosphatase 1 mutation in several organisms are not due to a failure to activate the APC. Contrary to this, the initiation of mitotic cyclin B proteolysis is prevented by inhibitors of protein phosphatase 2A such as okadaic acid. Okadaic acid induces an activity that inhibits cyclin B ubiquitination. We refer to this activity as inhibitor of mitotic proteolysis because it also prevents the degradation of other APC substrates. A similar activity exists in extracts of Xenopus eggs that are arrested at the second meiotic metaphase by the cytostatic factor activity of the protein kinase mos. In Xenopus eggs, the initiation of anaphase II may therefore be prevented by an inhibitor of APC-dependent ubiquitination.

Sign in / Sign up

Export Citation Format

Share Document