Seasonal and state-dependent changes of eIF4E and 4E-BP1 during mammalian hibernation: implications for the control of translation during torpor

被引:50
作者
van Breukelen, F
Sonenberg, N
Martin, SL [1 ]
机构
[1] Univ Colorado, Sch Med, Dept Cell & Dev Biol, Denver, CO 80262 USA
[2] Univ Colorado, Sch Med, Program Mol Biol, Denver, CO 80262 USA
[3] Univ Nevada, Dept Biol Sci, Las Vegas, NV 89154 USA
[4] McGill Univ, Dept Biochem, Montreal, PQ H3G 1Y6, Canada
[5] McGill Univ, McGill Canc Ctr, Montreal, PQ H3G 1Y6, Canada
关键词
eukaryotic initiation factor 4E; 4E binding protein-1; protein synthesis;
D O I
10.1152/ajpregu.00728.2003
中图分类号
Q4 [生理学];
学科分类号
071003 ;
摘要
Mammalian hibernation involves cessation of energetically costly processes typical of homeostatic regulation including protein synthesis. To further elucidate the mechanisms employed in depressing translation, we surveyed key eukaryotic initiation factors [eIF2, eIF4B, eIF4E, eIF4GI and -II, and 4E-binding protein-1 (4E-BP1), -2, and -3] for their availability and phosphorylation status in the livers of golden-mantled ground squirrels (Spermophilus lateralis) across the hibernation cycle. Western blot analyses indicated only one significant locus for regulation of translational initiation in ground squirrel liver: control of eIF4E. We found seasonal variation in a potent regulator of eIF4E activity, 4E-BP1. Summer squirrels lack 4E-BP1 and apparently control eIF4E activity through direct phosphorylation. In winter, eIF4E is regulated through binding with 4E-BP1. During the euthermic periods that separate bouts of torpor (interbout arousal), 4E-BP1 is hyperphosphorylated to promote initiation. However, during torpor, 4E-BP1 is hypophosphorylated and cap-dependent initiation of translation is restricted. The regulation of cap-dependent initiation of translation may allow for the differential expression of proteins directed toward enhancing survivorship.
引用
收藏
页码:R349 / R353
页数:5
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