Processing of the @entity28348 precursor @entity28349 to XXXX is critical for @entity5271 -induced osteoclast differentiation.

@entity28348 @entity1991 @entity33518 @entity19 @entity28349 @entity15385 @entity5271 @entity1993 @entity25314 @entity2525 @entity10179
Gene targeting of the @entity1991 and @entity28348 subunits of @entity1991 has shown that @entity1991 plays a critical role in osteoclast differentiation. However, the molecular mechanism by which @entity1991 regulates osteoclast differentiation is still unclear. To address this issue, we analyzed alymphoplasia ( @entity10179 / @entity10179 ) @entity19 in which the processing of @entity28349 to @entity28348 does not occur owing to an inactive form of @entity10179 ( @entity10179 ). @entity10179 / @entity10179 @entity19 showed a mild @entity2525 with significantly reduced osteoclast numbers. @entity5271 -induced osteoclastogenesis from bone marrow cells of @entity10179 / @entity10179 @entity19 also was suppressed. @entity5271 still induced the degradation of @entity1993 and activated classical @entity1991 , whereas processing of @entity28349 to @entity28348 was abolished by the @entity10179 / @entity10179 mutation. Moreover, @entity5271 -induced expression of @entity25314 was impaired in @entity10179 / @entity10179 bone marrow. Overexpression of constitutively active @entity15385 or @entity28348 restored osteoclastogenesis in @entity10179 / @entity10179 cells. Finally, transfection of either wild-type @entity28349 , @entity33518 GRR that cannot be processed to @entity28348 , or @entity28348 into @entity28348 -deficient cells followed by @entity5271 treatment revealed a strong correlation between the number of osteoclasts induced by @entity5271 and the ratio of @entity28348 to @entity28349 expression. Our data provide a new finding for a previously unappreciated role for @entity1991 in osteoclast differentiation.
