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a b s t r a c tBesides its canonical function of catalyzing the formation of telomeric repeats, many groups have recently reported non-canonical functions of hTERT in particular, and telomerase in general. Regulating transcription is the central basis of non-canonical functions of telomerase. However, unlike reverse transcriptase activity of telomerase that requires only a few molecules of enzymatically active hTERT, non-canonical functions of hTERT or other telomerase components theoretically require several hundred copies. Here, we provide the first direct quantification of all the telomerase components in human cancer cell lines. We demonstrate that telomerase components do not exist in a 1:1 stoichiometric ratio, and there are several hundred copies of hTERT in cells. This provides the molecular basis of hTERT to function in other signaling cascades, including transcription.

Cleaners in Taiwan are a high-risk group for developing MSDs, and solutions are needed to avoid extreme motion angles of the wrists when performing cleaning tasks. Moreover, both psychosocial stress and the welfare of this group of workers deserve immediate attention from management and the government.

What covalent modifications control the temporal ubiquitination of ERα and hence the duration of its transcriptional activity remain poorly understood. We show that GREB1, an ERα-inducible enzyme, catalyzes O-GlcNAcylation of ERα at residues T553/S554, which stabilizes ERα protein by inhibiting association with the ubiquitin ligase ZNF598. Loss of GREB1-mediated glycosylation of ERα results in reduced cellular ERα levels and insensitivity to estrogen. Higher GREB1 expression in ERα+ve breast cancer is associated with greater survival in response to tamoxifen, an ERα agonist. Mice lacking Greb1 exhibit growth and fertility defects reminiscent of phenotypes in ERα-null mice. In summary, this study identifies GREB1, a protein with an evolutionarily conserved domain related to DNA-modifying glycosyltransferases of bacteriophages and kinetoplastids, as the first inducible and the only other (apart from OGT) O-GlcNAc glycosyltransferase in mammalian cytoplasm and ERα as its first substrate.