Department of Biochemistry, Tohoku University Graduate School of Medicine, Sendai, Miyagi 980-8575, Japan.
Mol Cell. 2011 Mar 4;41(5):554-66. doi: 10.1016/j.molcel.2011.02.018.
Protein methylation pathways comprise methionine adenosyltransferase (MAT), which produces S-adenosylmethionine (SAM) and SAM-dependent substrate-specific methyltransferases. However, the function of MAT in the nucleus is largely unknown. MafK represses or activates expression of heme oxygenase-1 (HO-1) gene, depending on its heterodimer partners. Proteomics analysis of MafK revealed its interaction with MATIIα, a MAT isozyme. MATIIα was localized in nuclei and found to form a dense network with chromatin-related proteins including Swi/Snf and NuRD complexes. MATIIα was recruited to Maf recognition element (MARE) at HO-1 gene. When MATIIα was knocked down in murine hepatoma cell line, expression of HO-1 was derepressed at both basal and induced levels. The catalytic activity of MATIIα, as well as its interacting factors such as MATIIβ, BAF53a, CHD4, and PARP1, was required for HO-1 repression. MATII serves as a transcriptional corepressor of MafK by interacting with chromatin regulators and supplying SAM for methyltransferases.
蛋白质甲基化途径包括甲硫氨酸腺苷转移酶（MAT），它产生 S-腺苷甲硫氨酸（SAM）和 SAM 依赖性底物特异性甲基转移酶。然而，MAT 在核内的功能在很大程度上是未知的。MafK 根据其异二聚体伙伴抑制或激活血红素加氧酶-1（HO-1）基因的表达。MafK 的蛋白质组学分析显示其与 MATIIα（一种 MAT 同工酶）相互作用。MATIIα 定位于细胞核内，并与染色质相关蛋白（包括 Swi/Snf 和 NuRD 复合物）形成密集网络。MATIIα 被招募到 HO-1 基因的 Maf 识别元件（MARE）。当在鼠肝癌细胞系中敲低 MATIIα 时，HO-1 的表达在基础水平和诱导水平上均被去抑制。MATIIα 的催化活性以及其相互作用因子，如 MATIIβ、BAF53a、CHD4 和 PARP1，对于 HO-1 的抑制是必需的。MATII 通过与染色质调节剂相互作用并为甲基转移酶提供 SAM，充当 MafK 的转录共抑制因子。
