Degradation of unassembled Vph1p reveals novel aspects of the yeast ER quality control system

The endoplasmic reticulum quality control (ERQC) system retains and degrade s soluble and membrane proteins that misfold or fail to assemble. Vph1p is the 100 kDa membrane subunit of the yeast Saccharomyces cerevisiae V-ATPase , which together with other subunits, assembles into the V-ATPase in the ER , requiring the ER resident protein Vma22p, In vma22 Delta cells, Vph1p rem ains an integral membrane protein with wild-type topology in the ER membran e before undergoing a rapid and concerted degradation requiring neither vac uolar proteases nor transport to the Golgi, Failure to assemble targets Vph 1p for degradation in a process involving ubiquitylation, the proteasome an d cytosolic but not ER lumenal chaperones, Vph1p appears to possess the tra its of a 'classical' ERQC substrate, yet novel characteristics are involved in its degradation: (i) UBC genes other than UBC6 and UBC7 are involved an d (ii) components of the ERQC system identified to date (Der1p, Hrd1p/Der3p and Hrd3p) are not required, These data suggest that other ERQC components must exist to effect the degradation of Vph1p, perhaps comprising an alter native pathway.