ING1 has been reported to cooperate with p53 to inhibit cell proliferation. The precise effects of ING1 on cells that differ in the p53 status are not known. To shed light onto the function of ING1, isogenic H1299 cell lines were created that expressed ING1b (the major form of ING1 in these cells) and p53 either individually or in combination under inducible promoters. A 5-10 fold induction of ING1b in the absence of p53 exacerbated the G₂/M DNA damage checkpoint induced by Adriamycin, but did not affect the DNA damage responses mediated by cisplatin or UV. No significant transactivation of p21^CIP1/WAF1 and MDM2 by ING1b in the absence of p53 was observed, suggesting that mechanisms involving activation of p53-related proteins are unlikely to contribute to the actions of ING1b. Expressi...[ Read more ]

ING1 has been reported to cooperate with p53 to inhibit cell proliferation. The precise effects of ING1 on cells that differ in the p53 status are not known. To shed light onto the function of ING1, isogenic H1299 cell lines were created that expressed ING1b (the major form of ING1 in these cells) and p53 either individually or in combination under inducible promoters. A 5-10 fold induction of ING1b in the absence of p53 exacerbated the G₂/M DNA damage checkpoint induced by Adriamycin, but did not affect the DNA damage responses mediated by cisplatin or UV. No significant transactivation of p21^CIP1/WAF1 and MDM2 by ING1b in the absence of p53 was observed, suggesting that mechanisms involving activation of p53-related proteins are unlikely to contribute to the actions of ING1b. Expression of p53 in H1299 to a level comparable to the basal level in other p53-containing cells decreased proliferation. Evidence was shown that in a portion of cells, expression of this low level of p53 in the absence of DNA damage induced irreversible exit from the cell cycle. In contrast, co-expression of p53 and ING1b induced cell cycle arrest and allowed the cells to renter the cell cycle when p53 and ING1b were removed. In the presence of Adriamycin-mediated DNA damage, cell death induced by the cooperation between ING1b and p53 was much more prominent than the individual protein alone. These and other evidence presented here indicate that ING1b can cause cell cycle arrest or cell death through p53-dependent and independent mechanisms.