Investigation of Novel Human CED-4 Homolog NAC-X in Apoptosis Regulation of Breast Cancer

摘要

Proteins containing a Caspase-Associated Recruitment Domain (CARD) have previously been shown to-serve as key regulators of tumor cell survival as well as regulators of other- cellular processes, such as cytokine production. Interleukin-l beta (IL-1B) is a cytokine which has been found to be expressed in breast cancer cells and may be associated with more aggressive and invasive breast tumors. Here we report the cloning and functional characterization of NAC-X or CLAN (CARD, LRR, And NACHT-containing protein). CLAN was found to be expressed in several breast cancer cell lines as well as in monocytes by RT- PCR. Co-immunoprecipitation studies revealed that CLAN associated several other proteins including caspase-l, Nod2, and NAC. When assayed using an IL-1B ELISA, CLAN was found to induce the activation of caspase-l in response to bacterial infection or LPS, implying a role for this protein in the innate immune response. CLAN also was found to enhance cell death following bacterial infection independently of caspase-l. Through its interactions with other CARD- containing proteins, CLAN may regulate the survival of breast cancer cells and Could be utilized as a novel anti-tumor target or diagnostic/prognostic biomarker.