Cancers, Vol. 11, Pages 554: Complementary Roles of GCN5 and PCAF in Foxp3+ T-Regulatory Cells

Cancers, Vol. 11, Pages 554: Complementary Roles of GCN5 and PCAF in Foxp3+ T-Regulatory Cells Cancers doi: 10.3390/cancers11040554 Authors: Yujie Liu Chunrong Bao Liqing Wang Rongxiang Han Ulf H. Beier Tatiana Akimova Philip A. Cole Sharon Y. R. Dent Wayne W. Hancock Functions of the GCN5-related N-acetyltransferase (GNAT) family of histone/protein acetyltransferases (HATs) in Foxp3+ T-regulatory (Treg) cells are unexplored, despite the general importance of these enzymes in cell biology. We now show that two prototypical GNAT family members, GCN5 (general control nonrepressed-protein 5, lysine acetyltransferase (KAT)2a) and p300/CBP-associated factor (p300/CBP-associated factor (PCAF), Kat2b) contribute to Treg functions through partially distinct and partially overlapping mechanisms. Deletion of Gcn5 or PCAF did not affect Treg development or suppressive function in vitro, but did affect inducible Treg (iTreg) development, and in vivo, abrogated Treg-dependent allograft survival. Contrasting effects were seen upon targeting of each HAT in all T cells; mice lacking GCN5 showed prolonged allograft survival, suggesting this HAT might be a target for epigenetic therapy in allograft recipients, whereas transplants in mice lacking PCAF underwent acute allograft rejection. PCAF deletion also enhanced anti-tumor immunity in immunocompetent mice. Dual deletion of GCN5 and PCAF led to decreased Treg stability and numbers in peripheral lymphoid tissues, and mi...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Article Source Type: research