cdc25 is one of the MPM-2 antigens involved in the activation of maturation-promoting factor.

Kuang, Jian; Ashorn, Cheryl L.; Gonzalez-Kuyvenhoven, Mayra; Penkala, Joseph E.

doi:10.1091/mbc.5.2.135

Cited by 92 publications

(65 citation statements)

References 51 publications

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“…In the interphase-arrested extracts, H1 kinase activity remained low, the tyrosine-phosphorylated form of Cdc2 accumulated, cyclin B2 remained hypophosphorylated, Cdc25C did not undergo hyperphosphorylation, and nuclei continued to enlarge. In addition, M-phasespecific phosphoproteins were not detected with the MPM-2 antibody (Davis et al, 1989;Kuang et al, 1994;our unpublished results), providing further support that these extracts remained in interphase. The interphase arrest persisted for at least 130 min, even though control extracts had completed at least two cell cycles by this time.…”

Section: Discussion P42mapk Activation Inhibits Entry Into M-phase Inmentioning

confidence: 82%

Activation of the p42 Mitogen-activated Protein Kinase Pathway Inhibits Cdc2 Activation and Entry into M-Phase in CyclingXenopusEgg Extracts

Bitangcol

Chau

Stadnick

et al. 1998

MBoC

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We have added constitutively active MAP kinase/ERK kinase (MEK), an activator of the mitogen-activated protein kinase (MAPK) signaling pathway, to cycling Xenopus egg extracts at various times during the cell cycle. p42MAPK activation during entry into M-phase arrested the cell cycle in metaphase, as has been shown previously. Unexpectedly, p42MAPK activation during interphase inhibited entry into M-phase. In these interphase-arrested extracts, H1 kinase activity remained low, Cdc2 was tyrosine phosphorylated, and nuclei continued to enlarge. The interphase arrest was overcome by recombinant cyclin B. In other experiments, p42MAPK activation by MEK or by Mos inhibited Cdc2 activation by cyclin B. PD098059, a specific inhibitor of MEK, blocked the effects of MEK(QP) and Mos. Mos-induced activation of p42MAPK did not inhibit DNA replication. These results indicate that, in addition to the established role of p42MAPK activation in M-phase arrest, the inappropriate activation of p42MAPK during interphase prevents normal entry into M-phase.

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Section: Discussion P42mapk Activation Inhibits Entry Into M-phase Inmentioning

confidence: 82%

Activation of the p42 Mitogen-activated Protein Kinase Pathway Inhibits Cdc2 Activation and Entry into M-Phase in CyclingXenopusEgg Extracts

Bitangcol

Chau

Stadnick

et al. 1998

MBoC

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“…Two M-phase regulators of cdc2, the wee-1 tyrosine kinase and the cdc25 phosphatase (for review, see Coleman and Dunphy, 1994) are now proven MPM-2 phosphoproteins (Kuang et al, 1994;Mueller et al, 1995). It is reasonable to speculate that these proteins are candidate MPM-2 antigens in NFTcontaining neurons as well.…”

Section: Discussionmentioning

confidence: 99%

Aberrant Expression of Mitotic Cdc2/Cyclin B1 Kinase in Degenerating Neurons of Alzheimer’s Disease Brain

et al. 1997

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We have shown previously that M-phase phospho-epitopes accumulate in neuronal tau proteins incorporated into the hallmark neurofibrillary tangles (NFT) of Alzheimer's disease (AD). In M phase, the epitopes are produced by cdc2/cyclin B1 kinase by a highly conserved mechanism believed to be quiescent in terminally differentiated neurons of adult brain. To determine whether an M-phase mechanism is possible in AD neurons, we first investigated the presence of cdc2 and cyclin B1 in AD. Both proteins were enriched in neurons with NFT and in neurons susceptible to NFT. An antibody specific for catalytically active cdc2 stained numerous NFT-containing neurons in AD but did not react with normal neurons. Double-labeling studies showed that active cdc2 and cyclin B1 coexist in AD neurons and co-localize with AD-specific mitotic phosphoepitopes. Mitotic kinase purified from AD and normal brain, using the yeast p13suc1 protein as affinity ligand, showed higher histone H1 phosphorylation activity in AD. Accordingly, the levels of cdc2 and cyclin B1 in p13suc1 fractions from AD were higher than normal. Consistent with a physiological relationship between NFT and mitotic kinase, NFT proteins copurified with and became phosphorylated by the p13suc1-bound kinase in vitro. Furthermore, cdc2/cyclin B1 is the only one of several proline-directed kinases that created the TG/MC mitotic phospho-epitopes in recombinant tau in vitro. These findings suggest that aberrantly reexpressed cdc2/cyclin B1 in NFT-bearing neurons in AD brain contributes to the generation of M-phase phospho-epitopes in NFT. Key words: cdc2; cyclin B; p13suc1; neuronal degeneration; Alzheimer's disease; neurofibrillary tangleMarked neuronal loss in Alzheimer's disease (AD) is often preceded by deposition of neurofibrillary tangles (NFT) that contain hyperphosphorylated proteinaceous aggregates called paired helical filaments (PHF) (for review, see Terry et al., 1994) (Trojanowski et al., 1993). Although these lesions have been studied for decades, little is known about the biochemical mechanisms that produce them. We recently presented evidence that certain NFT-specific monoclonal antibodies (i.e., the TG and MC series) recognize phospho-epitopes that are of a mitotic nature, displaying a temporally restricted pattern of appearance during M phase in a variety of proliferating eukaryotic cells (Vincent et al., 1996). We also reported that the conserved M-phase MPM-2 phosphoepitope is abundant in NFT-containing neurons in AD, but is not detected in neurons of normal brain (Vincent et al., 1996). Based on these findings, we hypothesized that a mitotic posttranslational mechanism participates in the formation of NFT and the death of neurons in AD.To gather support for this hypothesis, we first isolated mitotic kinase from brain using the yeast p13suc1 protein as affinity ligand and compared the phosphorylation activity of the kinase from AD brain with that of normal brain. We found that mitotic kinase activity is elevated in AD brain in comparison with normal. We als...

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“…Mitotic entry is accompanied by the phosphorylation of several molecules, including mitotic protein monoclonal 2 (MPM-2), that may regulate the mitotic processes. 24,25 Immunostaining using antiphospho-Ser/Thr-Pro and MPM-2 antibody (05-368; EMD Millipore, Bedford, MA) showed that the number of cells at M phase was increased in WTmice 1 day after IRI compared with in KO mice, but it only accounted for a small fraction of the cells arrested at G2/M phase, indicating that most p-H3-positive cells were arrested at G2 phase (Supplemental Figure 4, B and C). Figure 6A).…”

Section: Loss Of P53 Reduced Cell Cycle Arrest After Irimentioning

confidence: 99%

Targeted Deletion of p53 in the Proximal Tubule Prevents Ischemic Renal Injury

Yuan¹,

Kim

Westphal³

et al. 2014

Journal of the American Society of Nephrology

101

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The contribution of p53 to kidney dysfunction, inflammation, and tubular cell death, hallmark features of ischemic renal injury (IRI), remains undefined. Here, we studied the role of proximal tubule cell (PTC)-specific p53 activation on the short-and long-term consequences of renal ischemia/reperfusion injury in mice. After IRI, mice with PTC-specific deletion of p53 (p53 knockout [KO]) had diminished whole-kidney expression levels of p53 and its target genes, improved renal function, which was shown by decreased plasma levels of creatinine and BUN, and attenuated renal histologic damage, oxidative stress, and infiltration of neutrophils and macrophages compared with wild-type mice. Notably, necrotic cell death was attenuated in p53 KO ischemic kidneys as well as oxidant-injured p53-deficient primary PTCs and pifithrin-a-treated PTC lines. Reduced oxidative stress and diminished expression of PARP1 and Bax in p53 KO ischemic kidneys may account for the decreased necrosis. Apoptosis and expression of proapoptotic p53 targets, including Bid and Siva, were also significantly reduced, and cell cycle arrest at the G2/M phase was attenuated in p53 KO ischemic kidneys. Furthermore, IRI-induced activation of TGF-b and the long-term development of inflammation and interstitial fibrosis were significantly reduced in p53 KO mice. In conclusion, specific deletion of p53 in the PTC protects kidneys from functional and histologic deterioration after IRI by decreasing necrosis, apoptosis, and inflammation and modulates the long-term sequelae of IRI by preventing interstitial fibrogenesis.

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cdc25 is one of the MPM-2 antigens involved in the activation of maturation-promoting factor.

Cited by 92 publications

References 51 publications

Activation of the p42 Mitogen-activated Protein Kinase Pathway Inhibits Cdc2 Activation and Entry into M-Phase in CyclingXenopusEgg Extracts

Activation of the p42 Mitogen-activated Protein Kinase Pathway Inhibits Cdc2 Activation and Entry into M-Phase in CyclingXenopusEgg Extracts

Aberrant Expression of Mitotic Cdc2/Cyclin B1 Kinase in Degenerating Neurons of Alzheimer’s Disease Brain

Targeted Deletion of p53 in the Proximal Tubule Prevents Ischemic Renal Injury

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