Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.6.1.44 (AGT)
 770 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

O6-alkylguanine has been known to be the major lesion in DNA for the cytotoxicity of alkylating agents and it is repaired by O6-Alkylguanine-DNA alkyltransferase (O6-AGT). To examine the relation of O6-AGT to the clinical characteristics in malignant melanoma (MM), O6-AGT activity in 13 human MM tissues was measured. The activity in tumor tissues varied widely from 0 to 0.11 pmol/mg protein. The activity in normal skin tissues was lower and less variable than in the tumors. The activity was not related to the tumor size or clinical stage of melanomas, but it was higher in tumors after chemotherapy with alkylating agents than in those without chemotherapy. In metastatic tissues, in primary tumors of the patients with metastases and in tumors of the patients with bad prognosis, the activity was also high. Two of the tumors, having the highest O6-AGT activity, were both transplantable to nude mice. These results suggest two possibilities; melanomas exposed to the alkylating agents may change to have high O6-AGT activity, followed by the resistance to such agents, or O6-AGT in melanomas may be originally diverse. O6-AGT activity in the tumour tissue may represent the effect of alkylating agents and can be used in selecting the methods of therapy.
J Dermatol Sci 1992 Jul
PMID:O6-alkylguanine-DNA alkyltransferase activity in human malignant melanoma. 139 Apr 58

Mutations in distinct sites of epidermal keratins, in particular in the helix initiation and termination regions, cause human genodermatoses due to faulty intermediate filament formation. Extension of this observation to human hereditary hair and nail diseases includes population analyses of human hair keratin genes for natural sequence variations in the corresponding sites. Here we report on a large-scale genotyping of the short helix termination region (HTR) of the human type I cortical hair keratins hHa1, a3-I, and a3-II, and the cuticular hair keratin hHa2. We describe two polymorphic loci, P1 and P2, exclusively in the cuticular hHa2 gene, both creating dimorphic protein variants. P1 is due to a C to T mutation in a CpG element leading to a threonine to methionine substitution; P2 concerns a serine codon AGT that also occurs as an asparagine coding variant AAC. A third polymorphism, P3, is linked with a C to T point mutation located at the very beginning of intron 6. The three polymorphic sites are clustered in a 39-nucleotide sequence of the hHa2 gene. Both allelic frequency calculations in individuals of different races and pedigree studies indicate that the two-allelic hHa2 variants resulting from P1 and P2 occur ubiquitously in a ratio of about 1:1 (P1) and 2:1 (P2) respectively in our survey, and are clearly inherited as Mendelian traits. A genotype carrying both mutations simultaneously on one allele could not be detected in our sampling, and there was no association of a distinct allelic hHa2 variant with the known ethnic form variations of hairs. Sequence comparisons of the HTR of hHa2 with those of other type I hair keratins including the hHa2-ortholog from chimpanzee provide evidence that the P1- and P2-linked mutations must have occurred very early in human evolution and that the two P2-associated codon variants may be the result of two independent point mutations in an ancestral AGC serine codon. These data describe natural polymorphisms in the HTR of a member of the keratin multigene family.
J Invest Dermatol 1996 Mar
PMID:The region coding for the helix termination motif and the adjacent intron 6 of the human type I hair keratin gene hHa2 contains three natural, closely spaced polymorphic sites. 864 91