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Example sentences for: fhit
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The human FHIT gene, located at the chromosome 3 fragile site FRA3B, is inactivated early in the development of many tumors [ 1 ] . Murine Fhit is also located at a fragile site [ 2 3 ] and mice heterozygous for disruption of Fhit , given low intragastric doses of the mutagen N-nitrosomethylbenzylamine, develop stomach and sebaceous tumors [ 4 ] that can be prevented by viral Fhit expression [ 5 ] . Fhit, a dimer of 147 amino acid subunits, is a member of the histidine triad (HIT) superfamily of nucleotide hydrolases and transferases [ 6 7 ] . Members of the Hint branch of the HIT superfamily are found in all forms of life [ 8 ] . The S. cerevisiae Hint homolog, Hnt1, and rabbit Hint possess adenosine monophosphoramidase activity that functions in yeast to positively regulate function of Kin28, Ccl1 and Tfb3, which constitute the kinase component of general transcription factor TFIIH [ 9 ] . A new Hint related protein, Aprataxin, is mutated in individuals with ataxia with oculomotor apraxia [ 10 11 ] and has a yeast homolog termed Hnt3 [ 9 ] . Members of the Fhit branch of the HIT superfamily have been found in fungi [ 12 13 ] , animals [ 2 14 15 ] and plants [ 7 ] and hydrolyze diadenosine tetraphosphate, diadenosine triphosphate and other 5'-5"'-dinucleoside polyphosphates.
4%) have also reported a similar overall high frequency of promoter methylation [ 12 13 ] . We identified promoter methylation in >25% cases in CDH1 , DAPK , and RARB genes, while it was less frequent (10-25% cases) in HIC1 , FHIT , RASSF1A , and APC genes in CC patients.
3 region to which RASSF1A maps undergoes deletions in many solid tumor types, including GCTs [ 9 ] . RASSF1A encodes a splice variant of human RAS effector homologue, which interacts with the XPA protein and functions as a negative regulator of cell growth [ 16 17 ] . RASSF1A has been shown to be inactivated by promoter methylation in a variety of tumor types [ 16 17 18 19 ] . The 17q21 and 17p13 regions, to which BRCA1 and HIC1 map, respectively, also have been characterized by high frequency of LOH in GCT [ 9 ] . The BRCA 1 gene plays critical roles in DNA repair and recombination, cell cycle checkpoint control, and transcription and has been shown to be hypermethylated in breast-ovarian cancer [ 4 ] . The HIC1 gene is also often hypermethylated in many human cancers [ 20 21 22 ] . The DNA repair gene MGMT encodes O(6)-methylguanine-DNA methyltransferase and this enzyme effectively removes DNA adducts formed by alkylating agents [ 23 ] . Epigenetic inactivation of the MGMT gene was reported in a wide variety of cancers [ 24 25 ] . Also, a low frequency of methylation of the APC , RARB , and FHIT genes was detected in NSGCTs.
Loss of Fhit protein is among the earliest known events in the development of a variety of the most common and lethal human malignancies [ 1 ] . Loss of Fhit leads to cells that are deficient in programmed cell death and that form tumors in mice while Fhit reexpression in Fhit-cancer cells reduces tumorigenicity and restores programmed cell death [ 2 3 4 5 6 ] . Infection of Fhit +/- mice with viruses that re-express Fhit reduce cancer occurrence [ 7 ] , apparently by killing pre-neoplastic cells that have lost the wild-type Fhit allele.
Given that neither transcriptional nor post-transcriptional regulation has been reported for Fhit protein, the level of biological activity of Fhit may be controlled by levels of Fhit substrates, inhibitors, and proteins that interact with Fhit-nucleotide complexes.
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