AUF1 (hnRNP D0)
中文名称
通路描述
AUF1 (hnRNP D0) 二聚体结合 mRNA 3'非翻译区 AU 富集元件 (AREs) 中的 U 富集区域。结合导致 AUF1 二聚体组装成更高阶的四聚体复合物。二磷酸化的 AUF1 结合 RNA 后招募其他蛋白质，包括 eIF4G、polyA 结合蛋白、热休克蛋白 (Hsp)、Hsc70、Hsp27、NSEP-1、NSAP-1 和 IMP-2，这些蛋白质靶向 mRNA 和 AUF1 进行降解。未磷酸化的 AUF1 被认为招募其他蛋白的能力较弱。AUF1 也直接与或间接地与 HuR 和 RNA 诱导的沉默复合物 (RISC) 相互作用。与 RNA 和其他蛋白质结合的 AUF1 被泛素化并靶向蛋白酶体降解，而结合的 mRNA 被降解。泛素化添加至 AUF1 的抑制可阻断 mRNA 降解。泛素依赖性蛋白水解与 mRNA 降解耦合的机制尚不清楚。AUF1 至少存在 4 个异构体：p45 (45 kDa) 包含所有外显子，p42 缺少外显子 2，p40 缺少外显子 7，p37 缺少外显子 2 和 7。p42 和 p45 中外显子 7 的存在似乎会阻断泛素化，而外显子 7 的缺失 (p37 和 p40) 则靶向 AUF1 进行泛素化并破坏结合的 RNA。缺少外显子 2 (p37 和 p42) 与对 RNA 和 14-3-3sigma (SFN) 的高亲和力相关。
英文描述
AUF1 (hnRNP D0) binds and destabilizes mRNA AUF1 (hnRNP D0) dimers bind U-rich regions of AU-rich elements (AREs) in the 3' untranslated regions of mRNAs. The binding causes AUF1 dimers to assemble into higher order tetrameric complexes. Diphosphorylated AUF1 bound to RNA recruits additional proteins, including eIF4G, polyA-binding protein, Hsp, Hsc70, Hsp27, NSEP-1, NSAP-1, and IMP-2 which target the mRNA and AUF1 for degradation. Unphosphorylated AUF1 is thought to be less able to recruit additional proteins. AUF1 also interacts directly or indirectly with HuR and the RNA-induced silencing complex (RISC).
AUF1 complexed with RNA and other proteins is ubiquitinated and targeted for destruction by the proteasome while the bound mRNA is degraded. Inhibition of ubiquitin addition to AUF1 blocks mRNA degradation. The mechanism by which ubiquitin-dependent proteolysis is coupled to mRNA degradation is unknown.
At least 4 isoforms of AUF1 exist: p45 (45 kDa) contains all exons, p42 lacks exon 2, p40 lacks exon 7, and p37 lacks exons 2 and 7. The presence of exon 7 in p42 and p45 seems to block ubiquitination while the absence of exon 7 (p37 and p40) targets AUF1 for ubiquitination and destabilizes bound RNAs. Lack of exon 2 (p37 and p42) is associated with higher affinity for RNA and 14-3-3sigma (SFN).
AUF1 binds and destabilizes mRNAs encoding Interleukin-1 beta (IL1B), Tumor Necrosis Factor alpha (TNFA), Cyclin-dependent kinase inhibitor 1 (CDNK1A, p21), Cyclin-D1 (CCND1), Granulocyte-macrophage colony stimulating factor (GM-CSF, CSF2), inducible Nitric oxide synthase (iNOS, NOS2), Proto-oncogene cFos (FOS), Myc proto-oncogene (MYC), Apoptosis regulator Bcl-2 (BCL2).
AUF1 complexed with RNA and other proteins is ubiquitinated and targeted for destruction by the proteasome while the bound mRNA is degraded. Inhibition of ubiquitin addition to AUF1 blocks mRNA degradation. The mechanism by which ubiquitin-dependent proteolysis is coupled to mRNA degradation is unknown.
At least 4 isoforms of AUF1 exist: p45 (45 kDa) contains all exons, p42 lacks exon 2, p40 lacks exon 7, and p37 lacks exons 2 and 7. The presence of exon 7 in p42 and p45 seems to block ubiquitination while the absence of exon 7 (p37 and p40) targets AUF1 for ubiquitination and destabilizes bound RNAs. Lack of exon 2 (p37 and p42) is associated with higher affinity for RNA and 14-3-3sigma (SFN).
AUF1 binds and destabilizes mRNAs encoding Interleukin-1 beta (IL1B), Tumor Necrosis Factor alpha (TNFA), Cyclin-dependent kinase inhibitor 1 (CDNK1A, p21), Cyclin-D1 (CCND1), Granulocyte-macrophage colony stimulating factor (GM-CSF, CSF2), inducible Nitric oxide synthase (iNOS, NOS2), Proto-oncogene cFos (FOS), Myc proto-oncogene (MYC), Apoptosis regulator Bcl-2 (BCL2).
所含基因
42 个基因