Six CDKN2A families had pancreatic cancer . They also show that families with the CDKN2A 113insArg mutation have an increased risk not only of multiple melanomas and pancreatic carcinoma but also of breast cancer. We previously described CDKN2A exon 2 mutations in a pilot study of 43 esophageal cancers.
Although germline CDKN2A coding mutations cosegregate with melanoma in 25-60% of families predisposed to the disease, there remains a number of mutation-negative families that demonstrate linkage of inherited melanoma to 9p21 markers. High frequency of multiple melanomas and breast and pancreas carcinomas in CDKN2A mutation-positive melanoma families.
CDKN2A (gene) has been shown to interact with SERTAD1, CCNG1, Death associated protein 6, P53, E4F1, Cyclin-dependent kinase 4, Cyclin-dependent kinase 6, Mdm2, RPL11 and PPP1R9B. In spite of their structural and functional differences, the CDK inhibitor isoforms and the ARF product encoded by this gene, through the regulatory roles of CDK4 and p53 in cell cycle G1 progression, share a common functionality in control of the G1 phase of the cell cycle. This gene is frequently mutated or deleted in a wide variety of tumors and is known to be an important tumor suppressor gene.
Function: BCHE Esterase with broad substrate specificity. Contributes to the inactivation of the neurotransmitter acetylcholine. Can degrade neurotoxic organophosphate esters.
Mutant alleles at the BCHE locus are responsible for suxamethonium sensitivity. Homozygous persons sustain prolonged apnea after administration of the muscle relaxant suxamethonium in connection with surgical anesthesia. The activity of pseudocholinesterase in the serum is low and its substrate behavior is atypical. In the absence of the relaxant, the homozygote is at no known disadvantage.
Overlapping drug interaction sites of human butyrylcholinesterase dissected by site-directed mutagenesis. Enzyme-linked immunosorbent assays for acetylcholinesterase (AChE) and for butyrylcholinesterase (BCHE) were markedly more specific than conventional assays using selective enzyme inhibitors. Butyrylcholinesterase in human brain and acetylcholinesterase in human plasma: trace enzymes measured by two-site immunoassay.
BCHE variants (BCHE and CHE2 Loci) associated with erythrocyte acetylcholinesterase inhibition in farmers exposed to pesticides. The findings do not support the premise that inhibitor therapy should target BuChE so as to prevent increased levels of BuChE from hydrolyzing acetylcholine in AD cerebral cortex. Thus, low BuChE in a patient's CSF may predict extensive incorporation in neuritic plaques, increased neurotoxicity and greater central neurodegeneration.
Transient expression of BCHE-reporter gene constructs showed that a 194-bp fragment of the 5'-flanking region of human BCHE and a 570-bp fragment of rabbit BCHE were sufficient for promoting chloramphenicol acetyltransferase activity in HeLa cells. The objectives of our study were to examine whether the BCHE K variant is associated with Type 2 diabetes or estimates of pancreatic beta cell function in large-scale populations of glucose-tolerant Caucasians.
An atypical form of butyrylcholinesterase or the absence of its activity leads to prolonged apnea following administration of the muscle relaxant suxamethonium. BCHE and obesity in individuals with the CHE2 C5+ and CHE2 C5- phenotypes. In this retrospective analysis, Alzheimer's disease patients younger than 75 with wild-type BuChE exhibited differential efficacy to rivastigmine, while BuChE K-variant carriers experienced similar long-term treatment effects with both agents.
Protein concentration and acetylcholinesterase (AChE) and butyrylcholinesterase (BCHE) activities were assayed in the cerebrospinal fluid (CSF) of 26 healthy normal subjects (20-86 years old), 27 patients with dementia of the Alzheimer type (DAT), and 10 patients with dementia of the Alzheimer type with extrapyramidal signs (EDAT). Scores of some of the neuropsychological tests associated with memory and attention were correlated with both plasma and CSF AChE and BuChE inhibition for up to 6 months. Pretreatment with wild-type BChE or A328W tetramers at a dose of 2.8 units/g i.p. reduced cocaine-induced locomotor activity by 50 and 80%.
