Abstract 2216: SUMOylated CPAP contributes to NF-kB activation in cancer cells

Nuclear factor kappa-B (NF-κB) is a transcription factor which involves in hepatocellular carcinoma (HCC). The development of therapeutic drugs to specifically target NF-κB signaling pathway is imperative to achieve. Centrosomal and P4.1-associated protein (CPAP) is a novel co-activator of NF-κB. The effects of CPAP on NF-κB activation pathway were determined by over-expression and knockdown approaches. CPAP increased the expression of NF-κB target genes by enhancing the transcriptional activaty of NF-κB. Through recruiting more IkappaB kinase beta (IKKα) to the inactivated NF-κB complex, CPAP augmented the phosphorylation of inhibitor of NF-κB (IαBβ) and NF-κB. Chromatin immunoprecipitation assay further showed that CPAP is recruited to IL-8 and ICAM-1 promoter under TNF-α treatment. CPAP was covalently modified by SUMO-1 (small ubiquitin-related modifier-1) protein at the C-terminal region. SUMO-deficient CPAP mutants lost the co-activator activity on NF-κB activation pathway and failed to enter the nucleus upon TNF-α treatment. By immunohistochemistry (IHC) analysis, CPAP was detected in the nucleus of HBV-associated HCC. Activation of NF-κB was synergically augmented by CPAP overexpression in HBx-expressing Hep3B (Hep3BX) and HepG2 (HepG2X) cells lines. SUMOylation of CPAP could modulate the activity of NF-κB, and CPAP may serve as a target for therapeutic purpose in HBV-associated HCC. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2216. doi:1538-7445.AM2012-2216