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Compound
Pivot Concepts:
Gene/Protein
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Target Concepts:
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Query: EC:2.7.10.1 (
ERK
)
95,504
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
Thyroid cancers are largely divided into medullary (MTC) and non-medullary (
NMTC
) cancers , depending on the cell type of origin. Familial non-medullary thyroid cancer (FNMTC) comprises about 5-15% of
NMTC
and is a heterogeneous group of diseases, including both non-syndromic and syndromic forms. Non-syndromic FNMTC tends to manifest papillary thyroid carcinoma , usually multifocal and bilateral . Several high-penetrance genes for FNMTC have been identified, but they are often confined to a few or single families, and other susceptibility loci appear to play a small part, conferring only small increments in risk. Familial susceptibility is likely to be due to a combination of genetic and environmental influences. The current focus of research in FNMTC is to characterise the susceptibility genes and their role in carcinogenesis. FNMTC can also occur as a part of multitumour genetic syndromes such as familial adenomatous polyposis , Cowden's disease , Werner's syndrome and Carney complex . These tend to present at an early age and are multicentric and bilateral with distinct pathology. The clinical evaluation of these patients is similar to that for most patients with a thyroid nodule. Medullary thyroid cancer (MTC) arises from the parafollicular cells of the thyroid which release calcitonin. The familial form of MTC accounts for 20-25% of cases and presents as a part of the multiple endocrine neoplasia type 2 (MEN 2) syndromes or as a pure familial MTC (FMTC). They are caused by germline point mutations in the
RET
oncogene on chromosome 10q11.2. There is a clear genotype-phenotype correlation, and the aggressiveness of FMTC depends on the specific genetic mutation, which should determine the timing of surgery.
...
PMID:Diagnosis and Management of Hereditary Thyroid Cancer. 2707 47
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