PDCD5 interacts with Tip60 and functions as a cooperator in acetyltransferase activity and DNA damage-induced apoptosis.
Tip60 is a histone acetyltransferase (HAT) involved in the acetyltransferase activity and the cellular response to DNA damage. Here, we show that programmed cell death 5 (PDCD5), a human apoptosis-related protein, binds to Tip60 and enhances the stability of Tip60 protein in unstressed conditions. The binding amount of PDCD5 and Tip60 is significantly increased after UV irradiation. Further, PDCD5 enhances HAT activity of Tip60 and Tip60-dependent histone acetylation in both basal and UV-induced levels. We also find that PDCD5 increases Tip60-dependent K120 acetylation of p53 and participates in the p53-dependent expression of apoptosis-related genes, such as Bax. Moreover, we demonstrate the biological significance of the PDCD5-Tip60 interaction; that is, they function in cooperation to accelerate DNA damage-induced apoptosis and knockdown of PDCD5 or Tip60 impairs their apoptosis-accelerating activity, mutually. Consistent with this, PDCD5 levels increase significantly on DNA damage in U2OS cells, as does Tip60. Together, our findings indicate that PDCD5 may play a dual role in the Tip60 pathway. Specifically, under normal growth conditions, PDCD5 contributes to maintaining a basal pool of Tip60 and its HAT activity. After DNA damage, PDCD5 functions as a Tip60 coactivator to promote apoptosis.
Xu
Lanjun
L
Laboratory of Medical Immunology, School of Basic Medical Sciences, Peking University Health Science Center, 38 Xueyuan Road, Beijing, 100191, China.
Chen
Yingyu
Y
Song
Quansheng
Q
Xu
Dong
D
Wang
Ying
Y
Ma
Dalong
D
D000107:Acetylation; D017209:Apoptosis / Q000502:physiology*; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism*; D015153:Blotting, Western; D004249:DNA Damage / Q000502:physiology*; D005455:Fluorescent Antibody Technique; D005786:Gene Expression Regulation / Q000502:physiology*; D051548:Histone Acetyltransferases / Q000378:metabolism*; D006801:Humans; D047468:Immunoprecipitation; D000074443:Lysine Acetyltransferase 5; D009363:Neoplasm Proteins / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014162:Transfection; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
D051017:Apoptosis Regulatory Proteins; D009363:Neoplasm Proteins; C117283:PDCD5 protein, human; D016159:Tumor Suppressor Protein p53; D051548:Histone Acetyltransferases; C098489:KAT5 protein, human; D000074443:Lysine Acetyltransferase 5