No abstract

Telomerase is believed to be induced upon proliferation and inhibited when cells differentiate. Thus, regulation of telomerase activity could be an important mechanism to limit growth of normal and cancer cells. Using transforming growth factor-beta 1 (TGF-β1), which is known to control proliferation in epithelial cells, we now demonstrate that in the human HaCaT skin keratinocytes, TGF-β1 downregulated c-Myc, and this blocked proliferation. This also caused a decrease in hTERT expression, which in turn inhibited telomerase activity. Overexpressing hTERT recovered telomerase activity but not proliferation, whereas constitutive expression of c-Myc recovered proliferation and hTERT expression. Nevertheless, telomerase remained inhibited, thus dissociating proliferation and telomerase activity. In addition, we show that TGF-β1 inhibited telomerase activity despite ongoing hTERT transcription by inducing loss of the full-length hTERT transcript (mediating telomerase activity) and retaining high expression of the inactive β variant. These changes in the splicing pattern reversed upon TGF-β1 removal, as did inhibition of telomerase activity, suggesting that alternative splicing may represent a novel mechanism of telomerase regulation by TGF-β1. In addition, we show that destruction of tissue integrity (in a model for epidermal blistering) resulted in a rapid induction of the inactive β variant, whereas tissue regeneration (formation of a stratified epithelium) correlated with a shift to the active full-length transcript, which is the dominant form in intact epidermis. Thus alternative splicing may not be restricted to TGF-β1 but may add a more general mechanism of hTERT regulation in epidermal cells.

-Compounds (III) and (V) are characterized by IR, Raman, and NMR spectroscopy, and by single crystal XRD. (III) crystallizes in the trigonal space group P3m1 with Z = 1 and (V) in the orthorhombic space group Pbcm with Z = 4. In the crystal structure of (III) the Hg 2+ ion is octahedrally coordinated by six N atoms of six [B(CN) 4 ] − anions. The structure of compound (V) contains Hg 2 2+ ions bridged via N atoms.

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ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.