A novel protein, RTN-x(S), interacts with both Bcl-x(L) and Bcl-2 on endoplasmic reticulum and reduces their anti-apoptotic activity

Bcl-2 and Bcl-x(L) serve as critical inhibitors of apoptosis triggered by a broad range of stimuli, mainly acting on the mitochondria, We identified t wo members of the reticulon (RTN) family as Bcl-x(L) binding proteins, i.e, , NSP-C (RTNt-C) and a new family member, RTN-x(S), both of which did not b elong to the Bcl-2 family and were predominantly localized on the endoplasm ic reticulum (ER). RTN-x(S) interacted with both Bcl-x(L) and Bcl-2, increa sed the localization of Bcl-xL and Bcl-2 on the ER, and reduced the anti-ap optotic activity of Bcl-xL and Bcl-2. On the other hand, NSP-C interacted o nly with Bcl-x(L), affected the localization of Bcl-x(L), and reduced Bcl-x L activity, but had no effect on Bcl-2, These results suggest that RTN fami ly proteins can modulate the anti-apoptotic activity of Bcl-x(L) and Bcl-2 by binding with them and can change their localization to the ER.