mz, I think my email is not functioning. These were the first two in the NIH link under telomerase.(Thanks Andy) I found the first interseting b/c the 54K protein may interfer w/ telomeric strutures. The second was interesting to me b/c the Whithead group seems to be ahead of GERN in the understanding of telomere subunits. Any comments?
squetch
J Virol 1997 Sep;71(9):6629-6640
Adenovirus type 12 early region 1B 54K protein significantly extends the
life span of normal mammalian cells in culture.
Gallimore PH, Lecane PS, Roberts S, Rookes SM, Grand RJ, Parkhill J
CRC Institute for Cancer Studies, Medical School, University of Birmingham, Edgbaston, United Kingdom.
p.h.gallimore@bham.ac.uk
The life span of normal human cells in culture is extended by two to four total life spans following retrovirus-mediated transfer
of the adenovirus type 12 E1B 54,000-molecular-weight protein (54K protein). This extension of the in vitro growth potential
was accomplished without any of the obvious changes in morphology or growth properties that are usually associated with viral
transformation. These 54K+ cells escape the normal senescence checkpoint (M1) and show a very extended secondary
growth phase. The 54K+ human cells eventually enter crisis (M2), which does not appear to be due to either telomere attrition
or the activation of the senescence-associated proteins p21SdilCipIWaf1 and p16INK4A. Even in the absence of telomerase
activity, high-molecular-weight heterogeneous telomeres are produced and maintained in both 54K+ adult dermal fibroblasts
and embryo kidney cells, indicating that the 54K protein may interfere with the normal metabolism of telomeric structures
during cell division. These findings are discussed with reference to the known ability of the 54K protein to influence p53
function.
Whitehead Institute for Biomedical Research and Department of Biology, Massachusetts Institute of Technology, Cambridge,
MA 02142
Telomerase is an RNA-directed DNA polymerase, composed of RNA and protein subunits, that replicates the telomere ends
of linear eukaryotic chromosomes. Using a genetic strategy described here, we identify the product of the EST2 gene, Est2p,
as a subunit of telomerase in the yeast Saccharomyces cerevisiae. Est2p is required for enzyme catalysis, as mutations in EST2
were found to result in the absence of telomerase activity. Immunochemical experiments show that Est2p is an integral subunit
of the telomerase enzyme. Critical catalytic residues present in RNA-directed DNA polymerases are conserved in Est2p; mutation of one such residue abolishes telomerase activity, suggesting a direct catalytic role for Est2p.
The life span of normal human cells in culture is extended by two to four total life spans following retrovirus-mediated transfer
of the adenovirus type 12 E1B 54,000-molecular-weight protein (54K protein). This extension of the in vitro growth potential
was accomplished without any of the obvious changes in morphology or growth properties that are usually associated with viral
transformation. These 54K+ cells escape the normal senescence checkpoint (M1) and show a very extended secondary
growth phase. The 54K+ human cells eventually enter crisis (M2), which does not appear to be due to either telomere attrition
or the activation of the senescence-associated proteins p21SdilCipIWaf1 and p16INK4A. Even in the absence of telomerase
activity, high-molecular-weight heterogeneous telomeres are produced and maintained in both 54K+ adult dermal fibroblasts
and embryo kidney cells, indicating that the 54K protein may interfere with the normal metabolism of telomeric structures
during cell division. These findings are discussed with reference to the known ability of the 54K protein to influence p53
function. |
