Abstract:
:Tuberous sclerosis (TSC) is a multi-system disorder characterized by hamartomatous tumors and abnormal brain development, with multiple foci of disrupted neuronal migration and giant dysmorphic neurons within cortical tubers. TSC is associated with mutations in 2 genes, TSC1 and TSC2, which encode hamartin and tuberin, respectively. The functions of these proteins have yet to be determined. Recently, the Drosophila homologue of TSC2, gigas, has been shown to be required for the G2/M transition of the cell cycle. However, the mechanism of this action remains unknown. Because the cyclin-dependent kinase CDK1 forms a complex with cyclin B1 to trigger the G2/M transition, we hypothesized that tuberin interacts with CDK1 to regulate its activity. In the study reported in this paper, we have used co-immunoprecipitation and confocal microscopy to demonstrate that tuberin interacts with and co-localizes with CDK1 and its binding partner cyclin B1 in multiple cell types. We also demonstrate that hamartin interacts with CDK1 and cyclin B1. We further present evidence that tuberin interacts with the other regulatory subunit of CDK1, cyclin A. These findings suggest a direct role for tuberin and hamartin in modulating the activity of CDK1 during G2 and the G2/M transition. This is the first description of a role for both tuberin and hamartin in a common cellular function, providing a potential mechanism for the identical clinicopathologic manifestations that result when either of these proteins are inactivated.
journal_name
J Neuropathol Exp Neuroljournal_title
Journal of neuropathology and experimental neurologyauthors
Catania MG,Mischel PS,Vinters HVdoi
10.1093/jnen/60.7.711subject
Has Abstractpub_date
2001-07-01 00:00:00pages
711-23issue
7eissn
0022-3069issn
1554-6578journal_volume
60pub_type
杂志文章abstract::Shigella dysenteriae strains produce an exotoxin (SdT) which inhibits protein synthesis in susceptible cells and is neurotoxic in some species. Intraneural microinjection of highly purified SdT into the cervical vagus nerves of rats, mice, guinea pigs and rabbits produced cytopathic changes within 24 hours in vagal se...
journal_title:Journal of neuropathology and experimental neurology
pub_type: 杂志文章
doi:10.1097/00005072-198509000-00005
更新日期:1985-09-01 00:00:00
abstract::Lewy body-like hyaline inclusions in the soma and swollen, cord-like cell processes are characteristic alterations of the anterior horn cells in familial amyotrophic lateral sclerosis (ALS) with posterior column and spinocerebellar tract involvement. A fine structural analysis of these two structures has been performe...
journal_title:Journal of neuropathology and experimental neurology
pub_type: 杂志文章
doi:10.1097/00005072-198409000-00002
更新日期:1984-09-01 00:00:00
abstract::Neurofibromatosis 2 (NF2), a dominantly inherited disorder, is typically manifested as bilateral vestibular Schwannomas and predisposes to other nervous system tumors. Vestibular Schwannomas also occur sporadically but the onset is usually at an older age. Surgical and histological studies have shown that vestibular S...
journal_title:Journal of neuropathology and experimental neurology
pub_type: 杂志文章
doi:10.1097/00005072-199511000-00004
更新日期:1995-11-01 00:00:00
abstract::Voltage-gated potassium channel complex (VGKC-complex) antibody (Ab) encephalitis is a well-recognized form of limbic encephalitis in humans, usually occurring in the absence of an underlying tumor. The patients have a subacute onset of seizures, magnetic resonance imaging findings suggestive of hippocampal inflammati...
journal_title:Journal of neuropathology and experimental neurology
pub_type: 杂志文章
doi:10.1097/NEN.0000000000000063
更新日期:2014-05-01 00:00:00
abstract::Fibrosis is the main cause of irreversible nerve damage in leprosy. Phenotypic changes in Mycobacterium leprae (ML)-infected Schwann cells (SCs) have been suggested to mediate this process. We found that SC line cultures stimulated with ML upregulated transforming growth factor-β1 (TGF-β1), and that TGF-β1 or ML induc...
journal_title:Journal of neuropathology and experimental neurology
pub_type: 杂志文章
doi:10.1097/NEN.0b013e31828bfc60
更新日期:2013-04-01 00:00:00
abstract::Little is known about the molecular features of desmoplastic infantile ganglioglioma (DIG) and desmoplastic infantile astrocytoma (DIA). We performed a genome-wide DNA copy number analysis in combination with a multiplex ligation-dependent probe amplification-based analysis of copy number changes of candidate genes in...
journal_title:Journal of neuropathology and experimental neurology
pub_type: 杂志文章
doi:10.1097/NEN.0b013e3182a033a0
更新日期:2013-09-01 00:00:00
abstract::Despite the key role of γ-aminobutyric acid (GABA) neurons in the modulation of cerebral cortical output, little is known about their development in the human cortex. We analyzed several GABAergic parameters in standardized regions of the cerebral cortex and white matter in a total of 38 human fetuses and infants from...
journal_title:Journal of neuropathology and experimental neurology
pub_type: 杂志文章
doi:10.1097/NEN.0b013e31822f471c
更新日期:2011-10-01 00:00:00
abstract::This study explores the biochemical basis that may distinguish neurologic and nonneurologic forms of Gaucher's disease. Crude membrane preparations from spleens of controls and patients representing the three clinical categories of Gaucher's disease were delipidated by extraction with sodium cholate and n-butanol. Tot...
journal_title:Journal of neuropathology and experimental neurology
pub_type: 杂志文章
doi:10.1097/00005072-198211000-00006
更新日期:1982-11-01 00:00:00
abstract::The present study introduces an in vitro model of xenogeneic peripheral nerve rejection to analyze the role of macrophages in this complex immunological situation. Nerve-sensitized mouse peritoneal exudate cells were co-cultured with rat peripheral nerve segments. The cultured rat nerve segments were fulminantly rejec...
journal_title:Journal of neuropathology and experimental neurology
pub_type: 杂志文章
doi:10.1097/00005072-199401000-00007
更新日期:1994-01-01 00:00:00
abstract::Acetylcholinesterase (AChE) activity has been studied in normal, control and denervated muscle of rabbits by electron microscopic-cytochemistry and radiometric assay. A small amount of butyrylcholinesterase (BuChE) activity is also found in biochemical assay of unfixed muscle, but it is not demonstrable cytochemically...
journal_title:Journal of neuropathology and experimental neurology
pub_type: 杂志文章
doi:10.1097/00005072-197703000-00004
更新日期:1977-03-01 00:00:00
abstract::Hydrocephalic hyh mice are born with moderate hydrocephalus and a normal cerebral aqueduct. At about the fifth postnatal day the aqueduct becomes obliterated and severe hydrocephalus develops. The aim of the present investigation was to investigate the mechanism of this hydrocephalus, probably starting during fetal li...
journal_title:Journal of neuropathology and experimental neurology
pub_type: 杂志文章
doi:10.1093/jnen/60.11.1105
更新日期:2001-11-01 00:00:00
abstract::A noninvasive photodynamic method has been developed to produce focal brain necrosis using porphyrin activated in vivo with laser light. After peripheral injection of the photosensitive porphyrin derivative, Photofrin I, mice were irradiated on the posterior lateral aspect of the head through the intact depilated scal...
journal_title:Journal of neuropathology and experimental neurology
pub_type: 杂志文章
doi:10.1097/00005072-198909000-00005
更新日期:1989-09-01 00:00:00
abstract::Reactive astrogliosis is associated with many pathologic processes in the central nervous system, including gliomas. The glycoprotein podoplanin (PDPN) is upregulated in malignant gliomas. Using a syngeneic intracranial glioma mouse model, we show that PDPN is highly expressed in a subset of glial fibrillary acidic pr...
journal_title:Journal of neuropathology and experimental neurology
pub_type: 杂志文章
doi:10.1097/NEN.0000000000000150
更新日期:2015-01-01 00:00:00
abstract::Neuron loss, synaptic decline, and spongiform change are the hallmarks of sporadic Creutzfeldt-Jakob disease (sCJD), and may be related to deficiencies in mitochondria, energy metabolism, and protein synthesis. To investigate these relationships, we determined the expression levels of genes encoding subunits of the 5 ...
journal_title:Journal of neuropathology and experimental neurology
pub_type: 杂志文章
doi:10.1093/jnen/nlw048
更新日期:2016-08-01 00:00:00
abstract::To determine whether arterial wall degeneration, in combination with hemodynamic insult, causes cerebral artery aneurysms in a dog model, we simulated the geometry and hemodynamics of a human artery by surgical reconstruction of both common carotid arteries in 12 dogs. The dogs were then randomly assigned to one of th...
journal_title:Journal of neuropathology and experimental neurology
pub_type: 杂志文章
doi:10.1097/NEN.0000000000000100
更新日期:2014-09-01 00:00:00
abstract::Mutations in the leucine-rich repeat kinase 2 gene (LRRK2) have been recently identified in families with autosomal-dominant late-onset Parkinson disease. We report that by reverse transcriptase-polymerase chain reaction, the mRNA of LRRK2 is expressed in soluble extracts of human brain, liver, and heart and in cultur...
journal_title:Journal of neuropathology and experimental neurology
pub_type: 杂志文章
doi:10.1097/01.jnen.0000235121.98052.54
更新日期:2006-10-01 00:00:00
abstract::G-protein coupled receptor kinases (GRKs) constitute a serine/threonine kinase family playing a major role in agonist-induced phosphorylation and desensitization of G-protein coupled receptors. Recently, GRK2 and GRK5 have been demonstrated to phosphorylate alpha-synuclein (Ser129) and other synuclein isoforms. We stu...
journal_title:Journal of neuropathology and experimental neurology
pub_type: 杂志文章
doi:10.1097/01.jnen.0000248542.82681.12
更新日期:2006-12-01 00:00:00
abstract::Programmed cell death (PCD) via apoptosis is characterized by nuclear pyknosis and fragmentation, and biochemically by oligonucleosomal cleavage of DNA. Apoptosis occurs in the developing nervous system, whereas its role in neurodegenerative diseases is still debated. Recognition of apoptotic cells has recently been f...
journal_title:Journal of neuropathology and experimental neurology
pub_type: 杂志文章
doi:10.1097/00005072-199411000-00008
更新日期:1994-11-01 00:00:00
abstract::There are phenotypic and functional differences between vascular endothelium from different tissues and between microvascular and macrovascular endothelial cells (ECs) from the same tissue. Relatively little is known about the human blood-nerve barrier (BNB). We report the development of an in vitro BNB model using pr...
journal_title:Journal of neuropathology and experimental neurology
pub_type: 杂志文章
doi:10.1097/NEN.0b013e3181c84a9a
更新日期:2010-01-01 00:00:00
abstract::The immunopathological findings and their effects upon the vascular permeability of the ciliary process, choroid plexus and renal glomeruli to intravenously injected 125I-bovine serum albumin (BSA) have been studied in 26 rats who survived a prolonged period of bovine serum albuminemia following the experimental chron...
journal_title:Journal of neuropathology and experimental neurology
pub_type: 杂志文章
doi:10.1097/00005072-197707000-00007
更新日期:1977-07-01 00:00:00
abstract::The favorable response of oligodendrogliomas correlates well with characteristic chromosomal losses, of which loss of the short arm of chromosome 1 is most predictive. Oligodendrogliomas are histopathologically heterogeneous tumors and, in addition to the classic honeycomb histology, fields of nonclassic histology are...
journal_title:Journal of neuropathology and experimental neurology
pub_type: 杂志文章
doi:10.1097/nen.0b013e31815c254d
更新日期:2007-12-01 00:00:00
abstract::Maternal cigarette smoking during pregnancy is associated with a significantly increased risk of Sudden Infant Death Syndrome (SIDS). This study investigated the effects of prenatal exposure to carbon monoxide (CO), a major component of cigarette smoke, on the neuroglial and neurochemical development of the medulla in...
journal_title:Journal of neuropathology and experimental neurology
pub_type: 杂志文章
doi:10.1093/jnen/59.3.218
更新日期:2000-03-01 00:00:00
abstract::Inclusion body myositis (IBM) is a late-onset inflammatory myopathy with distinctive clinical and histopathological features. The molecular basis for the disease remains unknown, but abnormal nuclear morphology and the accumulation of a protein that binds single-stranded DNA in a sequence-independent fashion suggest a...
journal_title:Journal of neuropathology and experimental neurology
pub_type: 杂志文章
doi:10.1097/00005072-199805000-00003
更新日期:1998-05-01 00:00:00
abstract::Lymphocytic choriomeningitis virus-induced central nervous system disease is characterized by death during a seizure approximately seven days after intracerebral inoculation. This process is mediated by thymus dependent lymphocytes, sensitized against viral antigens. Various forms of immunosuppressive treatment preven...
journal_title:Journal of neuropathology and experimental neurology
pub_type: 杂志文章
doi:10.1097/00005072-197701000-00003
更新日期:1977-01-01 00:00:00
abstract::The formation of Lewy bodies (LBs) and their relationship to other types of nigral inclusions associated with Parkinson disease (PD), such as pale bodies (PBs), remain poorly understood. Known constituents of LBs include alpha-synuclein (alphaS) and ubiquitin (Ub), providing windows to their morphogenesis. Additionall...
journal_title:Journal of neuropathology and experimental neurology
pub_type: 杂志文章
doi:10.1093/jnen/62.12.1241
更新日期:2003-12-01 00:00:00
abstract::Diabetic polyneuropathy (DPN) shows more severe functional and structural changes in type 1 than in type 2 human and experimental diabetes. We have previously suggested that these differences may be due to insulin and/or C-peptide deficiencies in type 1 diabetes. To further explore these differences between type I and...
journal_title:Journal of neuropathology and experimental neurology
pub_type: 杂志文章
doi:10.1093/jnen/62.3.260
更新日期:2003-03-01 00:00:00
abstract::A direct causal relationship between a human DNA virus, adeno serotype 12, and malignant transformation in target cells (sensory retinal neuronal precursors) was suggested by the development of a remarkably uniform retinoblastoma-like neoplasm in rats. In order to focus upon incipient photoreceptor differentiation, 27...
journal_title:Journal of neuropathology and experimental neurology
pub_type: 杂志文章
doi:10.1097/00005072-197501000-00003
更新日期:1975-01-01 00:00:00
abstract::Vanishing white matter disease (VWM) is a progressive cavitating disease of central white matter due to a deficiency of the translation initiation factor eIF2B. Oligodendrocytes appear to be numerically increased in some white matter areas, while decreased in others. We compared oligodendrocytes of cerebral, cerebella...
journal_title:Journal of neuropathology and experimental neurology
pub_type: 杂志文章
doi:10.1093/jnen/63.6.618
更新日期:2004-06-01 00:00:00
abstract::The effect of experimental obstructive jaundice on the oxidative status of brain tissues in rats was examined. Twenty-four male Wistar rats were divided into 4 groups: Group I was the control, group II was the sham operated, and groups III and IV were bile duct ligated and killed on the 5th and the 10th day, respectiv...
journal_title:Journal of neuropathology and experimental neurology
pub_type: 杂志文章
doi:10.1097/01.jnen.0000200152.98259.4e
更新日期:2006-02-01 00:00:00
abstract::The medulla was sampled from nine cases of sudden infant death syndrome (SIDS) and from six age-matched control cases without neurological disease. Morphometric analyses were performed on serial Nissl sections through the hypoglossal nucleus on the left side of the medulla. The total volume of the nucleus and both the...
journal_title:Journal of neuropathology and experimental neurology
pub_type: 杂志文章
doi:10.1097/00005072-199509000-00003
更新日期:1995-09-01 00:00:00