Flick Karin, Ouni Ikram, Wohlschlegel James A, Capati Chrissy, McDonald W Hayes, Yates John R, Kaiser Peter
Department of Biological Chemistry, University of California Irvine, Irvine, CA 92697, USA.
Nat Cell Biol. 2004 Jul;6(7):634-41. doi: 10.1038/ncb1143. Epub 2004 Jun 20.
The ubiquitin ligase SCF(Met30) is required for cell cycle progression in budding yeast. The critical function of SCF(Met30) is inactivation of the transcriptional activator Met4. Here we show that a single ubiquitin chain is attached to Met4 through lysine at position 163. Inhibition of Met4 ubiquitination by mutating lysine to arginine at this position constitutively activates, but does not stabilize, Met4. This supports a proteolysis-independent role of Cdc34-SCF(Met30)-catalysed Met4 ubiquitination. Surprisingly, the ubiquitin chain attached to Met4 is linked through Lys 48 in ubiquitin, a ubiquitin chain structure that is usually required for substrate targeting to the 26S proteasome. These results suggest that Lys 48-linked ubiquitin chains can have a regulatory role independent of proteolysis.
泛素连接酶SCF(Met30)是芽殖酵母细胞周期进程所必需的。SCF(Met30)的关键功能是使转录激活因子Met4失活。在此我们表明，单个泛素链通过第163位的赖氨酸连接到Met4上。通过将该位置的赖氨酸突变为精氨酸来抑制Met4泛素化会组成性地激活Met4，但不会使其稳定。这支持了Cdc34-SCF(Met30)催化的Met4泛素化具有不依赖于蛋白酶体降解的作用。令人惊讶的是，连接到Met4上的泛素链是通过泛素中的赖氨酸48连接的，这种泛素链结构通常是底物靶向26S蛋白酶体所必需的。这些结果表明，赖氨酸48连接的泛素链可以具有独立于蛋白酶体降解的调节作用。
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