Imataka H, Olsen H S, Sonenberg N
Department of Biochemistry and McGill Cancer Centre, McGill University, Montreal, Quebec, Canada.
EMBO J. 1997 Feb 17;16(4):817-25. doi: 10.1093/emboj/16.4.817.
Translation initiation in eukaryotes is facilitated by the cap structure, m7GpppN (where N is any nucleotide). Eukaryotic translation initiation factor 4F (eIF4F) is a cap binding protein complex that consists of three subunits: eIF4A, eIF4E and eIF4G. eIF4G interacts directly with eIF4E and eIF4A. The binding site of eIF4E resides in the N-terminal third of eIF4G, while eIF4A and eIF3 binding sites are present in the C-terminal two-thirds. Here, we describe a new eukaryotic translational regulator (hereafter called p97) which exhibits 28% identity to the C-terminal two-thirds of eIF4G. p97 mRNA has no initiator AUG and translation starts exclusively at a GUG codon. The GUG-initiated open reading frame (907 amino acids) has no canonical eIF4E binding site. p97 binds to eIF4A and eIF3, but not to eIF4E. Transient transfection experiments show that p97 suppresses both cap-dependent and independent translation, while eIF4G supports both translation pathways. Furthermore, inducible expression of p97 reduces overall protein synthesis. These results suggest that p97 functions as a general repressor of translation by forming translationally inactive complexes that include eIF4A and eIF3, but exclude eIF4E.
真核生物中的翻译起始由帽结构m7GpppN（其中N为任意核苷酸）促进。真核生物翻译起始因子4F（eIF4F）是一种帽结合蛋白复合物，由三个亚基组成：eIF4A、eIF4E和eIF4G。eIF4G直接与eIF4E和eIF4A相互作用。eIF4E的结合位点位于eIF4G的N端三分之一处，而eIF4A和eIF3的结合位点位于C端三分之二处。在此，我们描述了一种新的真核生物翻译调节因子（以下称为p97），它与eIF4G的C端三分之二具有28%的同源性。p97 mRNA没有起始AUG，翻译仅从GUG密码子开始。由GUG起始的开放阅读框（907个氨基酸）没有典型的eIF4E结合位点。p97与eIF4A和eIF3结合，但不与eIF4E结合。瞬时转染实验表明，p97抑制帽依赖性和非依赖性翻译，而eIF4G支持这两种翻译途径。此外，p97的诱导表达降低了整体蛋白质合成。这些结果表明，p97通过形成包括eIF4A和eIF3但不包括eIF4E的无翻译活性的复合物，作为翻译的一般抑制因子发挥作用。
