Department of Biochemistry, Robert Wood Johnson Medical School, Piscataway, New Jersey 08854, USA.
J Biol Chem. 2011 Jan 28;286(4):3104-18. doi: 10.1074/jbc.M110.135863. Epub 2010 Nov 12.
The evidence that nuclear proteins can be degraded by cytosolic proteasomes has received considerable experimental support. However, the presence of proteasome subunits in the nucleus also suggests that protein degradation could occur within this organelle. We determined that Sts1 can target proteasomes to the nucleus and facilitate the degradation of a nuclear protein. Specific sts1 mutants showed reduced nuclear proteasomes at the nonpermissive temperature. In contrast, high expression of Sts1 increased the levels of nuclear proteasomes. Sts1 targets proteasomes to the nucleus by interacting with Srp1, a nuclear import factor that binds nuclear localization signals. Deletion of the NLS in Sts1 prevented its interaction with Srp1 and caused proteasome mislocalization. In agreement with this observation, a mutation in Srp1 that weakened its interaction with Sts1 also reduced nuclear targeting of proteasomes. We reported that Sts1 could suppress growth and proteolytic defects of rad23Δ rpn10Δ. We show here that Sts1 suppresses a previously undetected proteasome localization defect in this mutant. Taken together, these findings explain the suppression of rad23Δ rpn10Δ by Sts1 and suggest that the degradation of nuclear substrates requires efficient proteasome localization.
核蛋白可以被胞质中的蛋白酶体降解这一证据已经得到了大量实验的支持。然而，蛋白酶体亚基在核内的存在也表明蛋白降解可能发生在这个细胞器内。我们发现 Sts1 可以将蛋白酶体靶向细胞核，并促进核内蛋白的降解。在非允许温度下，特定的 sts1 突变体显示出核蛋白酶体减少。相比之下，Sts1 的高表达增加了核蛋白酶体的水平。Sts1 通过与 Srp1 相互作用将蛋白酶体靶向细胞核，Srp1 是一种结合核定位信号的核输入因子。Sts1 中 NLS 的缺失阻止了它与 Srp1 的相互作用，并导致蛋白酶体定位错误。与这一观察结果一致，Srp1 中的一个突变削弱了它与 Sts1 的相互作用，也减少了蛋白酶体的核靶向。我们曾报道过 Sts1 可以抑制 rad23Δ rpn10Δ 的生长和蛋白水解缺陷。我们在这里表明，Sts1 可以抑制该突变体中以前未检测到的蛋白酶体定位缺陷。总之，这些发现解释了 Sts1 对 rad23Δ rpn10Δ 的抑制作用，并表明核底物的降解需要有效的蛋白酶体定位。
