p53 is a central factor in
tumor suppression as exemplified by its frequent loss in human
cancer. p53 exerts its
tumor suppressive effects in multiple ways, but the ability to invoke the eradication of damaged cells by programmed cell death is considered a key factor. The ways in which p53 promotes cell death can involve direct activation or engagement of the cell death machinery, or can be via indirect mechanisms, for example though regulation of ER stress and autophagy. We present here another level of control in p53-mediated
tumor suppression by showing that p53 activates the
glycosidase, FUCA1, a modulator of N-linked glycosylation. We show that p53 transcriptionally activates FUCA1 and that p53 modulates
fucosidase activity via FUCA1 up-regulation. Importantly, we also report that chemotherapeutic drugs induce FUCA1 and
fucosidase activity in a p53-dependent manner. In this context, while we found that over-expression of FUCA1 does not induce cell death, RNAi-mediated knockdown of endogenous FUCA1 significantly attenuates p53-dependent,
chemotherapy-induced apoptotic death. In summary, these findings add an additional component to p53s
tumor suppressive response and highlight another mechanism by which the
tumor suppressor controls programmed cell death that could potentially be exploited for
cancer therapy.