Linked Life Data

21258399

Source:http://linkedlifedata.com/resource/pubmed/id/21258399

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
20
pubmed:dateCreated
2011-5-19
pubmed:abstractText
Malignant melanoma is an aggressive cancer known for its notorious resistance to most current therapies. The basic helix-loop-helix microphthalmia transcription factor (MITF) is the master regulator determining the identity and properties of the melanocyte lineage, and is regarded as a lineage-specific 'oncogene' that has a critical role in the pathogenesis of melanoma. MITF promotes melanoma cell proliferation, whereas sustained supression of MITF expression leads to senescence. By combining chromatin immunoprecipitation coupled to high throughput sequencing (ChIP-seq) and RNA sequencing analyses, we show that MITF directly regulates a set of genes required for DNA replication, repair and mitosis. Our results reveal how loss of MITF regulates mitotic fidelity, and through defective replication and repair induces DNA damage, ultimately ending in cellular senescence. These findings reveal a lineage-specific control of DNA replication and mitosis by MITF, providing new avenues for therapeutic intervention in melanoma. The identification of MITF-binding sites and gene-regulatory networks establish a framework for understanding oncogenic basic helix-loop-helix factors such as N-myc or TFE3 in other cancers.
pubmed:commentsCorrections
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
1476-5594
pubmed:author
pubmed:issnType
Electronic
pubmed:day
19
pubmed:volume
30
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2319-32
pubmed:meshHeading
pubmed:year
2011
pubmed:articleTitle
Essential role of microphthalmia transcription factor for DNA replication, mitosis and genomic stability in melanoma.
pubmed:affiliation
Institut de Génétique et de Biologie Moléculaire et Cellulaire, CNRS, INSERM, Université de Strasbourg, Illkirch, France.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't