Is NF-κB2/p100 a direct activator of programmed cell death?

Transcription factor NF-κB has been implicated in cancer development due to its ability to upregulate expression of genes with potentially prooncogenic functions, such as cell cycle regulators and antiapoptotic proteins (Karin et al., 2002). A recent report by Wang et al. (2002) suggests that a structural motif, a death domain (DD), present in one of the mammalian NF-κB proteins, NF-κB2/p100, allows it to directly activate cell death in a transcription-independent manner. Further, it is suggested that loss of the proapoptotic function of NF-κB2/p100 is directly linked to its oncogenic activity in lymphomas.