DISPLACEMENT OF HOUSEKEEPING PROTEASOME SUBUNITS BY MHC-ENCODED LMPS - A NEWLY DISCOVERED MECHANISM FOR MODULATING THE MULTICATALYTIC PROTEINASE COMPLEX
DISPLACEMENT OF HOUSEKEEPING PROTEASOME SUBUNITS BY MHC-ENCODED LMPS - A NEWLY DISCOVERED MECHANISM FOR MODULATING THE MULTICATALYTIC PROTEINASE COMPLEX
复制标题
DOI：
10.1002/j.1460-2075.1994.tb06625.x
复制
发表时间：
1994-07-15
期刊：
影响因子：
11.4
通讯作者：
YANG, Y
中科院分区：
文献类型：
--
作者：
FRUH, K;GOSSEN, M;YANG, Y
细胞质抗原降解为由I类MHC分子呈递的肽被认为是由泛素/蛋白酶体途径介导的。支持这一观点来自我们的观察，蛋白酶体的亚基组成可以改变干扰素-γ（IFN-γ）治疗。因此，在MHC II类区域中编码的两个亚基LMP 2和LMP 7被并入蛋白酶体复合物中，而其他亚基消失。在本通讯中报道的实验中，我们研究了细胞系中发生的亚基变化，其中LMP 2或LMP 7的表达可以通过IFN-γ诱导或通过应用新系统来控制转染的LMPs的表达来单独调节。在这两种情况下，LMP 2诱导只导致管家亚基2的消失，而LMP 7只影响亚基10。发现亚基2与LMP 2具有76%的同源性。由于将LMP 2掺入蛋白酶体复合物中可以防止亚基2前体的加工，因此我们得出结论，LMP 2在组装过程中取代了亚基2。亚基置换最有可能是调节蛋白酶体复合物的催化活性而不改变其结构的一般机制。此外，转染的亚基到复合物的控制掺入提供了一种新的方法来研究体内蛋白酶体功能。
The degradation of cytoplasmic antigens to peptides presented by class I MHC molecules is thought to be mediated by the ubiquitin/proteasome pathway. Support for this view came from our observation that the subunit composition of proteasomes can be changed by interferon-gamma (IFN-gamma) treatment. Thereby two subunits, LMP2 and LMP7, which are encoded in the MHC class II region, are incorporated into the proteasomal complex, whereas other subunits disappear. In the experiments reported in this communication we studied the subunit changes occurring in cell lines where the expression of LMP2 or LMP7 can be regulated individually either by IFN-gamma induction or by applying a new system to control the expression of transfected LMPs. In both situations LMP2 induction leads exclusively to the disappearance of housekeeping subunit 2, whereas LMP7 affects only subunit 10. Subunit 2 was found to be 76% homologous to LMP2. Since incorporation of LMP2 into the proteasomal complex prevents processing of the subunit 2 precursor, we conclude that LMP2 displaces subunit 2 during assembly. Subunit displacement is most likely a general mechanism to modulate the catalytic activity of the proteasomal complex without changing its structure. Furthermore, the controlled incorporation of transfected subunits into the complex offers a new approach to study proteasome function in vivo.