3.3 | DSG induced UHRF1 protein degradation, but did
not reduce mRNA levels
To investigate the effects of L7G and DSG on UHRF1 protein, we treated
PC3 cells with different concentrations of DSG or L7G for 48 hours, and
assessed the protein and mRNA levels of UHRF1. As shown in Fig. 3a and
Fig. 3b, L7G simultaneously reduced the levels of protein and mRNA of
UHRF1, while DSG only reduced the protein of UHRF1, did not reduce the
mRNA level. Consistently, DSG dramatically induced UHRF1 protein
degradation, but did not change mRNA levels in C4-2 and DU145 (Fig.
3c-d). We speculated that DSG might directly bind to UHRF1 protein
through TTD domain, and induced protein degradation of UHRF1. The
results indicated that DSG reduced UHRF1 expression through a
post-translational mechanism. Additionally, DSG greatly elevated the
protein level of p21, a typical downstream molecule of UHRF1, but had no
impact on the protein level of HDAC1. Since HDAC1 inhibitors have been
reported to elevate p21 level (Lagger, et al., 2002), we speculate that
DSG specifically reduced UHRF1 expression in PCa cells.