Veterans Administration Medical Center Research, White River Junction, VT 05009, USA.
Wiley Interdiscip Rev RNA. 2010 Sep-Oct;1(2):240-52. doi: 10.1002/wrna.11. Epub 2010 May 14.
The proteasome is a critical regulator of protein levels within the cell and is essential for maintaining homeostasis. A functional proteasome is required for effective mRNA surveillance and turnover. During transcription, the proteasome localizes to sites of DNA breaks, degrading RNA polymerase II and terminating transcription. For fully transcribed and processed messages, cytoplasmic surveillance is initiated with the pioneer round of translation. The proteasome is recruited to messages bearing premature termination codons, which trigger nonsense-mediated decay (NMD), as well as messages lacking a termination codon, which trigger nonstop decay, to degrade the aberrant protein produced from these messages. A number of proteins involved in mRNA translation are regulated in part by proteasome-mediated decay, including the initiation factors eIF4G, eIF4E, and eIF3a, and the poly(A)-binding protein (PABP) interacting protein, Paip2. eIF4E-BP (4E-BP) is differentially regulated by the proteasome: truncated to generate a protein with higher eIF4B binding or completely degraded, depending on its phosphorylation status. Finally, a functional proteasome is required for AU-rich-element (ARE)-mediated decay but the specific role the proteasome plays is unclear. There is data indicating the proteasome can bind to AREs, act as an endonuclease, and degrade ARE-binding proteins. How these events interact with the 5'-to-3' and 3'-to-5' decay pathways is unclear at this time; however, data is provided indicating that proteasomes colocalize with Xrn1 and the exosome RNases Rrp44 and Rrp6 in untreated HeLa cells.
蛋白酶体是细胞内蛋白质水平的关键调节因子，对于维持内稳态至关重要。功能正常的蛋白酶体对于有效的 mRNA 监测和周转是必需的。在转录过程中，蛋白酶体定位于 DNA 断裂部位，降解 RNA 聚合酶 II 并终止转录。对于完全转录和加工的消息，细胞质监测从翻译的先驱回合开始。蛋白酶体被招募到携带终止密码子的消息，这会触发无意义介导的衰变 (NMD)，以及缺乏终止密码子的消息，这会触发非停止衰变，以降解这些消息产生的异常蛋白质。许多参与 mRNA 翻译的蛋白质部分受到蛋白酶体介导的降解的调节，包括起始因子 eIF4G、eIF4E 和 eIF3a，以及 poly(A)-结合蛋白 (PABP) 相互作用蛋白 Paip2。eIF4E-BP (4E-BP) 被蛋白酶体以不同的方式调节：截短以生成与 eIF4B 结合更高的蛋白质，或完全降解，这取决于其磷酸化状态。最后，功能正常的蛋白酶体对于 AU 丰富元件 (ARE)-介导的衰变是必需的，但蛋白酶体具体的作用尚不清楚。有数据表明，蛋白酶体可以与 ARE 结合，作为内切核酸酶，并降解 ARE 结合蛋白。这些事件如何与 5'-至-3'和 3'-至-5'衰变途径相互作用，目前尚不清楚；然而，有数据表明，蛋白酶体与 Xrn1 和 exosome RNases Rrp44 和 Rrp6 在未处理的 HeLa 细胞中共定位。
