Fig. 6: Partial signaling pathways reported based on specific cell types by POGLUT1 for cell proliferation and inhibition.

Dual role of POGLUT1 in cell cycle progression or supression is cell-type specific. Up to now, a complete signaling pathway for cell proliferation or inhibition in response to overexpression of POGLUT1 is not fully explained; however, POGLUT1’ association with Notch and TGF-β1 signaling pathways has been observed. A In U937 and endometrial cancer cells, higher expression of POGLUT1 increases Notch signaling and HES-1 level, which in turn decreases P27 level without altering p15 and p16, and induces cell cycle progression or tumorigenesis. B Evidently, decreased expression level of p16 upon overexpressing POGLUT1 has also been observed, which explains the involvement of more than one signaling route in regulating CDKIs level. Upregulated POGLUT1 reduces Smad3 phosphorylation in breast cancer cells by repressing p16 expression in the presence of TGF-β1, thus promoting BT474 cell proliferation. C In contrast, overexpression of POGLUT1 in 293TRex cells triggers cell cycle arrest and increases Smad3 protein stability via inhibiting its proteasomal degradation. In fact, POGLUT1 enhances TGF-β1 signaling by modulating Smad3 expression and increases level of CDKIs p27 and p21, which bind with CDKs enzymes to block cell proliferation.