Acetylation of Sirt2 by p300 attenuates its deacetylase activity.
Histone deacetylases (HDACs) are subdivided into three classes--HDAC I, HDAC II, and Sir2. Sirt proteins are mammalian members of the Sir2 family of NAD+ (nicotinamide adenine dinucleotide)-dependent protein deacetylases. The balance between acetylation and deacetylation of histone and non-histone proteins, regulated by protein acetyltransferases and deacetylases, affects the expression of genes involved in a variety of cellular processes. In addition, HDAC1 is acetylated and regulated by p300, a transcriptional co-activator with protein acetyltransferase activity, suggesting that protein acetyltransferases and deacetylases they control the activities of each other. Although the regulation of HDAC1 by p300 is well characterized, the relationship between Sir2 homologs and p300 is not understood. Here, we report that p300 interacts with Sirt2, a member of the Sir2 family, and triggers the acetylation and subsequent down-regulation of the deacetylation activity of Sirt2, and that the acetylation of Sirt2 by p300 relieves the inhibitory effect of Sirt2 on the transcriptional activity of p53. These observations demonstrate that p300 can inactivate Sirt2 by acetylation and that p300 may regulate the activity of p53 indirectly through Sirt2 in addition to its direct modification of p53.
Han
Younho
Y
College of Pharmacy and Research Institute of Drug Development, Chonnam National University, Yongbong-dong 300, Gwangju 500-757, Republic of Korea.
Jin
Yun-Hye
YH
Kim
Yeon-Jin
YJ
Kang
Bok-Yun
BY
Choi
Hyun-Jin
HJ
Kim
Dae-Won
DW
Yeo
Chang-Yeol
CY
Lee
Kwang-Youl
KY
D000107:Acetylation; D002460:Cell Line; D015536:Down-Regulation; D056572:Histone Deacetylase Inhibitors; D006655:Histone Deacetylases / Q000378:metabolism*; D006801:Humans; D025941:Protein Interaction Mapping; D017434:Protein Structure, Tertiary; D056565:Sirtuin 2; D037761:Sirtuins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D050880:p300-CBP Transcription Factors / Q000235:genetics / Q000378:metabolism*; D000099224:p300-CBP-Associated Factor
D056572:Histone Deacetylase Inhibitors; D006655:Histone Deacetylases; D056565:Sirtuin 2; D037761:Sirtuins; D016159:Tumor Suppressor Protein p53; D050880:p300-CBP Transcription Factors; D000099224:p300-CBP-Associated Factor; C474199:SIRT2 protein, human