During preparation of the paper, an initial characterization of DRAM2 was reported [17]. According to the report, DRAM2 localizes in the lysosome, however DRAM2 was not found to regulate autophagy [17]. Although we have not directly addressed whether DRAM2 is involved in autophagy, we have shown that the level of LC3-II is increased upon DRAM2 expression. Since co-expression of DRAM2 with DRAM synergistically increased the level of LC3-II protein, it
INCB 018424 is quite possible that DRAM2 is associated with DRAM-mediated autophagy. It should also be noted that the co-expression of DRAM and DRAM2 resulted in a dramatic induction of cell death, while the individual
expression of either one of these proteins did not have this effect. As excessive autophagy can result in cell death [4] and [18], the co-expression of DRAM and DRAM2 may result in the onset of excessive autophagy, thereby causing cell death. Thus, we suggest that there is a functional interaction between DRAM2 and DRAM and that this interaction is involved in cell proliferation and cell death. Further research will be required to elucidate the unique functions of DRAM2.
