Linked Life Data

17556368

Source:http://linkedlifedata.com/resource/pubmed/id/17556368

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
34
pubmed:dateCreated
2007-8-20
pubmed:abstractText
Birt-Hogg-Dube (BHD) is a tumor suppressor gene disorder characterized by skin hamartomas, cystic lung disease, and renal cell carcinoma. The fact that hamartomas, lung cysts, and renal cell carcinoma can also occur in tuberous sclerosis complex (TSC) suggests that the BHD and TSC proteins may function within a common pathway. To evaluate this hypothesis, we deleted the BHD homolog in Schizosaccharomyces pombe. Expression profiling revealed that six permease and transporter genes, known to be down-regulated in Deltatsc1 and Deltatsc2, were up-regulated in Deltabhd, and levels of specific intracellular amino acids known to be low in Deltatsc1 and Deltatsc2 were elevated in Deltabhd. This "opposite" profile was unexpected, given the overlapping clinical phenotypes. The TSC1/2 proteins inhibit Rheb in mammals, and Tsc1/Tsc2 inhibit Rhb1 in S. pombe. Expression of a hypomorphic allele of rhb1(+) dramatically increased permease expression levels in Deltabhd but not in wild-type yeast. Loss of Bhd sensitized yeast to rapamycin-induced increases in permease expression levels, and rapamycin induced lethality in Deltabhd yeast expressing the hypomorphic Rhb1 allele. In S. pombe, it is known that Rhb1 binds Tor2, and Tor2 inhibition leads to up-regulation of permeases including those that are regulated by Bhd. Our data, therefore, suggest that Bhd activates Tor2. If the mammalian BHD protein, folliculin, similarly activates mammalian target of rapamycin, it will be of great interest to determine how mammalian target of rapamycin inhibition in BHD patients and mammalian target of rapamycin activation in TSC patients lead to overlapping clinical phenotypes.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
24
pubmed:volume
282
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
24583-90
pubmed:dateRevised
2007-12-3
pubmed:meshHeading
pubmed-meshheading:17556368-Alleles, pubmed-meshheading:17556368-Amino Acid Sequence, pubmed-meshheading:17556368-Amino Acids, pubmed-meshheading:17556368-Animals, pubmed-meshheading:17556368-Canavanine, pubmed-meshheading:17556368-Ethionine, pubmed-meshheading:17556368-Gene Expression Regulation, Fungal, pubmed-meshheading:17556368-Humans, pubmed-meshheading:17556368-Models, Biological, pubmed-meshheading:17556368-Molecular Sequence Data, pubmed-meshheading:17556368-Phenotype, pubmed-meshheading:17556368-Proteins, pubmed-meshheading:17556368-Proto-Oncogene Proteins, pubmed-meshheading:17556368-Schizosaccharomyces, pubmed-meshheading:17556368-Schizosaccharomyces pombe Proteins, pubmed-meshheading:17556368-Sequence Homology, Amino Acid, pubmed-meshheading:17556368-Tumor Suppressor Proteins
pubmed:year
2007
pubmed:articleTitle
The Birt-Hogg-Dube and tuberous sclerosis complex homologs have opposing roles in amino acid homeostasis in Schizosaccharomyces pombe.
pubmed:affiliation
Fox Chase Cancer Center, Philadelphia, Pennsylvania 19111, USA.
pubmed:publicationType
Journal Article, Research Support, N.I.H., Extramural