Spermidine/Spermine N1-Acetyltransferase 2 (SSAT2) functions as a coactivator for NF-kappaB and cooperates with CBP and P/CAF to enhance NF-kappaB-dependent transcription.
Activation of transcription by NF-kappaB requires association with coactivator proteins, including CBP/p300 and P/CAF. To identify new coregulatory proteins, a cytoplasmic two-hybrid screen was performed using the C-terminus of the p65 subunit as bait. Through this screen, the spermidine/spermine N(1)-acetyltransferase 2 (SSAT2) protein was identified as a potential modulator of NF-kappaB activity. SSAT2 was originally identified based on homology to SSAT1, a protein involved in polyamine catabolism. However both proteins contain an acetyltransferase domain that has similarity to the acetyltransferase domains of the GNAT superfamily of coactivators. Although SSAT2 is 46% identical to SSAT1, based on a recent report, SSAT2 does not appear to function in polyamine catabolism. Because of the similarity of SSAT2 to coactivators, we wanted to determine if SSAT2 could function as a coactivator for NF-kappaB. Coimmunoprecipitations confirmed the interaction between p65 and SSAT2. In transient transfection reporter gene assays, SSAT2 functions as a transcriptional coactivator for NF-kappaB and cooperates with CBP and P/CAF to enhance TNFalpha-induced NF-kappaB activity. Moreover, SSAT2 transiently associates with the promoters of the NF-kappaB-regulated cIAP2 and IL-8 genes in response to TNFalpha. Although the overall function of SSAT2 is not known, it appears that it can function as a transcriptional coactivator.
Vogel
Nancy L
NL
Department of Biological Sciences, MS 601, The University of Toledo, 2801 W. Bancroft St., Toledo, OH 43606, USA.
Boeke
Marta
M
Ashburner
Brian P
BP
D000123:Acetyltransferases / Q000378:metabolism*; D002460:Cell Line; D006801:Humans; D047468:Immunoprecipitation; D016328:NF-kappa B / Q000502:physiology*; D014158:Transcription, Genetic / Q000502:physiology*; D020798:Two-Hybrid System Techniques; D050880:p300-CBP Transcription Factors / Q000502:physiology*; D000099228:Diamine N-Acetyltransferase
D000123:Acetyltransferases; D016328:NF-kappa B; D050880:p300-CBP Transcription Factors; D000099228:Diamine N-Acetyltransferase