Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
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Drug
Enzyme
Compound
Query: UMLS:C0004134 (
ataxia
)
15,886
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
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.
...
PMID:Involvement of H4(D10S170) protein in ATM-dependent response to DNA damage. 1742 Jul 23
