ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2002
Pituitary adenylate cyclase activating polypeptide anti-mitogenic signaling in cerebral cortical progenitors is regulated by p57Kip2-dependent CDK2 activity.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2002. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
What it found
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The trial behind it
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Who cites it
33 citing papers in PubMed, 78 citations in OpenAlex.
- Divide or Commit - Revisiting the Role of Cell Cycle Regulators in Adult Hippocampal Neurogenesis.Frontiers in cell and developmental biology · 2019Review
- The Neuropeptides Vasoactive Intestinal Peptide and Pituitary Adenylate Cyclase-Activating Polypeptide Control HIV-1 Infection in Macrophages Through Activation of Protein Kinases A and C.Frontiers in immunology · 2018Article
- CyclinD1 and p57Oncotarget · 2017Article
- Role of ZAC1 in transient neonatal diabetes mellitus and glucose metabolism.World journal of biological chemistry · 2015Review
- Imprinted Zac1 in neural stem cells.World journal of stem cells · 2015Review
- Pleiotropic functions of pituitary adenylyl cyclase-activating polypeptide on retinal ontogenesis: involvement of KLF4 in the control of progenitor cell proliferation.Journal of molecular neuroscience : MN · 2014Article
- Engrailed2 modulates cerebellar granule neuron precursor proliferation, differentiation and insulin-like growth factor 1 signaling during postnatal development.Molecular autism · 2014Article
- Pituitary adenylate cyclase-activating polypeptide (PACAP) promotes both survival and neuritogenesis in PC12 cells through activation of nuclear factor κB (NF-κB) pathway: involvement of extracellular signal-regulated kinase (ERK), calcium, and c-REL.The Journal of biological chemistry · 2013Article
- Pro- and anti-mitogenic actions of pituitary adenylate cyclase-activating polypeptide in developing cerebral cortex: potential mediation by developmental switch of PAC1 receptor mRNA isoforms.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2013Article
- N-acetyl cysteine treatment reduces mercury-induced neurotoxicity in the developing rat hippocampus.Journal of neuroscience research · 2012Article
- Pituitary adenylyl cyclase-activating peptide counteracts hedgehog-dependent motor neuron production in mouse embryonic stem cell cultures.Journal of neuroscience research · 2011Article
- The cyclin-dependent kinase inhibitor p57Kip2 regulates cell cycle exit, differentiation, and migration of embryonic cerebral cortical precursors.Cerebral cortex (New York, N.Y. : 1991) · 2011Article
- S phase entry causes homocysteine-induced death while ataxia telangiectasia and Rad3 related protein functions anti-apoptotically to protect neurons.Brain : a journal of neurology · 2010Article
- Pituitary adenylate cyclase-activating polypeptide (PACAP)/PAC1HOP1 receptor activation coordinates multiple neurotrophic signaling pathways: Akt activation through phosphatidylinositol 3-kinase gamma and vesicle endocytosis for neuronal survival.The Journal of biological chemistry · 2010Article
- Integrating microRNA and mRNA expression profiles of neuronal progenitors to identify regulatory networks underlying the onset of cortical neurogenesis.BMC neuroscience · 2009Article
- Lot1 is a key element of the pituitary adenylate cyclase-activating polypeptide (PACAP)/cyclic AMP pathway that negatively regulates neuronal precursor proliferation.The Journal of biological chemistry · 2009Article
- PACAP signaling to DREAM: a cAMP-dependent pathway that regulates cortical astrogliogenesis.Molecular neurobiology · 2009Review
- Insulin-like growth factor-1 promotes G(1)/S cell cycle progression through bidirectional regulation of cyclins and cyclin-dependent kinase inhibitors via the phosphatidylinositol 3-kinase/Akt pathway in developing rat cerebral cortex.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2009Article
- PACAP38 protects rat cortical neurons against the neurotoxicity evoked by sodium nitroprusside and thrombin.Regulatory peptides · 2009Article
- Patterns of p57Kip2 expression in embryonic rat brain suggest roles in progenitor cell cycle exit and neuronal differentiation.Developmental neurobiology · 2009Article
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 2 countries.
Funding
Abstract
Generation of distinct cell types and numbers in developing cerebral cortex is subject to regulation by extracellular factors that positively or negatively control precursor proliferation. Although signals stimulating proliferation are well described, factors halting cell cycle progression are less well defined. At the molecular level, production and association of cyclins, cyclin-dependent kinases (CDKs), and CDK inhibitors (CKIs) regulate cycle progression. We now report that the endogenous peptide, pituitary adenylate cyclase activating polypeptide (PACAP), negatively regulates the cell cycle by inhibiting p57Kip2-dependent CDK2 activity in embryonic cortex. Protein levels of CDK2 and members of the CIP/KIP family of CKIs (p27Kip1, p57Kip2) were detected in developing rat cortex from embryonic day 13.5 through postnatal day 2. With advancing development, CDK2 protein levels decreased, whereas CKI expression increased, suggesting that stimulatory and inhibitory cycle proteins control cell cycle exit. Using a well defined, nonsynchronized, 8 hr precursor culture, PACAP decreased the fraction of cells crossing the G1/S boundary, inhibiting DNA synthesis by 35%. CDK2 kinase activity was inhibited 75% by PACAP, whereas kinase protein and its regulatory cyclin E subunit were unaffected. Moreover, decreased kinase activity was accompanied by a twofold increase in levels of p57Kip2 protein, but not p21Cip1 or p27Kip1, suggesting that p57Kip2 mediates PACAP anti-mitogenic effects. Indeed, immunoprecipitation of CDK2 complex revealed increased p57Kip2 association with the kinase and concomitant reduction in free inhibitor after PACAP exposure, suggesting that p57Kip2 interactions directly regulate CDK2 activity. These observations establish a mechanism whereby anti-mitogenic signals actively induce cell cycle withdrawal in developing cortex.
Indexed as
Identifiers
11880488PMC6758902W2135547475What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.