Linked Life Data

17420723

Source:http://linkedlifedata.com/resource/pubmed/id/17420723

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
42
pubmed:dateCreated
2007-9-13
pubmed:abstractText
H4(D10S170) gene has been identified upon its frequent rearrangement with RET in papillary thyroid tumours (RET/PTC1). The kinase ataxia telangectasia mutated (ATM) phosphorylates a limited number of downstream protein targets in response to DNA damage. We investigated the potential role of H4(D10S170) in DNA damage signaling pathways. We found that in cells treated with etoposide or ionizing radiation (IR), H4(D10S170) underwent ATM-mediated phosphorylation at Thr 434, stabilizing nuclear H4. In ataxia telangectasia cells (A-T), endogenous H4(D10S170) was localized to cytoplasm and was excluded from the nucleus. Moreover, H4(D10S170) was not phosphorylated in ATM-deficient lymphoblasts after ionizing irradiation. Inhibition of ATM kinase interfered with H4(D10S170) apoptotic activity, and expression of H4 with threonine 434 mutated in Alanine, H4(T434A), protected the cells from genotoxic stress-induced apoptosis. Most importantly, after exposure to IR we found that silencing of H4(D10S170) in mammalian cells increased cell survival, as shown by clonogenic assay, allows for DNA synthesis as evaluated by bromodeoxyuridine incorporation and permits cells to progress into mitosis as demonstrated by phosphorylation on Histone H3. Our results suggest that H4(D10S170) is involved in cellular response to DNA damage ATM-mediated, and that the impairment of H4(D10S170) gene function might have a role in thyroid carcinogenesis.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
0950-9232
pubmed:author
pubmed:issnType
Print
pubmed:day
13
pubmed:volume
26
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
6167-75
pubmed:dateRevised
2011-11-2
pubmed:meshHeading
pubmed:year
2007
pubmed:articleTitle
Involvement of H4(D10S170) protein in ATM-dependent response to DNA damage.
pubmed:affiliation
Dipartimento di Biologia e Patologia Cellulare e Molecolare, University 'Federico II', Naples, Italy.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't