Genes for human general transcription initiation factors TFIIIB, TFIIIB-associated proteins, TFIIIC2 and PTF/SNAPC: functional and positional candidates for tumour predisposition or inherited genetic diseases?
M. Purrello et al., Genes for human general transcription initiation factors TFIIIB, TFIIIB-associated proteins, TFIIIC2 and PTF/SNAPC: functional and positional candidates for tumour predisposition or inherited genetic diseases?, ONCOGENE, 20(35), 2001, pp. 4877-4883
TFIIIB, TFIIIC2, and PTF/SNAPC are heteromultimeric general transcription f
actors (GTFs) needed for expression of genes encoding small cytoplasmic (sc
RNAs) and small nuclear RNAs (snRNAs). Their activity is stimulated by vira
l oncogenes, such as SV40 large T antigen and Adenovirus EIA, and is repres
sed by specific transcription factors (STFs) acting as antioncogenes, such
as p53 and pRb. GTFs role as final targets of critical signal transduction
pathways, that control cell proliferation and differentiation, and their in
volvement in gene expression regulation suggest that the genes encoding the
m are potential proto-oncogenes or anti-oncogenes or may be otherwise invol
ved in the pathogenesis of inherited genetic diseases. To test our hypothes
is through the positional candidate gene approach, we have determined the p
hysical localization in the human genome of the 11 genes, encoding the subu
nits of these GTFs, and of three genes for proteins associated with TFIIIB
(GTF3BAPs). Our data, obtained by chromosomal in situ hybridization, radiat
ion hybrids and somatic cell hybrids analysis, demonstrate that these genes
are present in the human genome as single copy sequences and that some clu
ster to the same cytogenetic band, alone or in combination with class II GT
Fs. Intriguingly, some of them are localized within chromosomal regions whe
re recurrent, cytogenetically detectable mutations are seen in specific neo
plasias, such as neuroblastoma, uterine leyomioma, mucoepidermoid carcinoma
of the salivary glands and hemangiopericytoma, or where mutations causing
inherited genetic diseases map, such as Peutz-Jeghers syndrome. Their molec
ular function and genomic position make these GTF genes interesting candida
tes for causal involvement in oncogenesis or in the pathogenesis of inherit
ed genetic diseases.