Linked Life Data

11280020

Source:http://linkedlifedata.com/resource/pubmed/id/11280020

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:dateCreated
2001-3-30
pubmed:abstractText
The limited proliferative potential of normal cells in culture, cell replicative senescence, is an accepted model for ageing at the cellular level. Tumour-derived, or viral- or carcinogen-transformed cells have escaped senescence and proliferate without control (immortal). We and others have found that fusion of normal with immortal human cells yields hybrids that have regained growth control and cease division. This demonstrates that the phenotype of replicative senescence is dominant and that cells immortalize because of defects in senescence-related genes. We exploited the recessive nature of immortality and by fusing different immortal cell lines with each other identified four complementation groups for indefinite division. Immortal parental cell lines with similar senescence gene defects when fused yielded hybrids with unlimited division potential and were assigned to the same complementation group. Fusion of immortal cell lines with different gene defects resulted in complementation in the hybrids, which had limited division capability. These parental cell lines were assigned to different complementation groups. Using microcell-mediated chromosome transfer, we then demonstrated that introduction of a normal human chromosome 4 induced senescence only in immortal cell lines assigned to complementation group B. We have now cloned the gene on chromosome 4, MORF4 (mortality factor on chromosome 4). It is a member of a family of seven genes and only MORF4 and the MORF-related genes MRG15 and MRGX are expressed. The predicted protein motifs strongly suggest this is a novel family of transcription factors. We have identified interacting proteins, some of which are also novel. These genes have the potential to modulate expression of a large number of genes by chromatin remodelling. They, therefore, also have the potential to affect tissue function due to changes in expression activity during ageing.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:issn
1528-2511
pubmed:author
pubmed:issnType
Print
pubmed:volume
235
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
105-10; discussion 110-5; 146-9
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
2001
pubmed:articleTitle
Identification of genes involved in cell senescence and immortalization: potential implications for tissue ageing.
pubmed:affiliation
Huffington Center on Aging, Baylor College of Medicine, M320, One Baylor Plaza, Houston, TX 77030, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Review