DEGRADATION OF SUBUNITS OF THE SEC61P COMPLEX, AN INTEGRAL COMPONENT OF THE ER MEMBRANE, BY THE UBIQUITIN-PROTEASOME PATHWAY

We have investigated the degradation of subunits of the trimeric Sec61 p complex, a key component of the protein translocation apparatus of t he ER membrane, A mutant form of Sec61p and one of the two associated proteins (Sss1p) are selectively degraded, while the third constituent of the complex (Sbh1p) is stable, Our results demonstrate that the pr oteolysis of the multispanning membrane protein Sec61p is mediated by the ubiquitin-proteasome pathway, since it requires polyubiquitination , the presence of a membrane-bound (Ubc6) and a soluble (Ubc7) ubiquit in-conjugating enzyme and a functional proteasome. The process is prop osed to be specific for unassembled Sec61p and Sss1p, Thus, our result s suggest that one pathway of ER degradation of abnormal or unassemble d membrane proteins is initiated at the cytoplasmic side of the ER.