Linked Life Data

15899810

Source:http://linkedlifedata.com/resource/pubmed/id/15899810

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
10
pubmed:dateCreated
2005-5-18
pubmed:abstractText
C19ORF5 is a sequence homologue of microtubule-associated proteins MAP1A/MAP1B of unknown function, except for its association with mitochondria-associated proteins and the paclitaxel-like microtubule stabilizer and candidate tumor suppressor RASSF1A. Here, we show that when overexpressed in mammalian cells the recombinant 393-amino acid residue COOH terminus of C19ORF5 (C19ORF5C) exhibited four types of distribution patterns proportional to expression level. Although normally distributed throughout the cytosol without microtubular association, C19ORF5C specifically accumulated on stabilized microtubules in paclitaxel-treated cells and interacted directly with paclitaxel-stabilized microtubules in vitro. The native 113-kDa full-length C19ORF5 and a shorter 56-kDa form similarly associated with stabilized microtubules in liver cells and stabilized microtubules from their lysates. As C19ORF5 accumulated, it appeared on mitochondria and progressively induced distinct perinuclear aggregates of mitochondria. C19ORF5 overlapped with cytochrome c-deficient mitochondria with reduced membrane potential. Mitochondrial aggregation resulted in gross degradation of DNA, a cell death-related process we refer to as mitochondrial aggregation and genome destruction (MAGD). Deletion mutagenesis revealed that the C19ORF5 hyperstabilized microtubule-binding domain resides in a highly basic sequence of <100 residues, whereas the MAGD activity resides further downstream in a distinct 25-residue sequence (F967-A991). Our results suggest that C19ORF5 mediates communication between the microtubular cytoskeleton and mitochondria in control of cell death and defective genome destruction through distinct bifunctional structural domains. The accumulation of C19ORF5 and resultant MAGD signaled by hyperstabilized microtubules may be involved in the tumor suppression activity of RASSF1A, a natural microtubule stabilizer and interaction partner with C19ORF5, and the taxoid drug family.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
0008-5472
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
65
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
4191-201
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed-meshheading:15899810-Amino Acid Sequence, pubmed-meshheading:15899810-Animals, pubmed-meshheading:15899810-COS Cells, pubmed-meshheading:15899810-Cercopithecus aethiops, pubmed-meshheading:15899810-Cytosol, pubmed-meshheading:15899810-DNA, pubmed-meshheading:15899810-Genome, pubmed-meshheading:15899810-Humans, pubmed-meshheading:15899810-Liver, pubmed-meshheading:15899810-Microtubule-Associated Proteins, pubmed-meshheading:15899810-Microtubules, pubmed-meshheading:15899810-Mitochondria, pubmed-meshheading:15899810-Molecular Sequence Data, pubmed-meshheading:15899810-Nerve Tissue Proteins, pubmed-meshheading:15899810-Paclitaxel, pubmed-meshheading:15899810-Protein Structure, Tertiary, pubmed-meshheading:15899810-Sequence Homology, Amino Acid, pubmed-meshheading:15899810-Transfection, pubmed-meshheading:15899810-Tubulin
pubmed:year
2005
pubmed:articleTitle
Distinct structural domains within C19ORF5 support association with stabilized microtubules and mitochondrial aggregation and genome destruction.
pubmed:affiliation
Center for Cancer Biology and Nutrition, Institute of Biosciences and Technology, Texas A&M University System Health Science Center, Houston, Texas 77030, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural