After cessation of lactation, involution of the @entity19 mammary gland proceeds in two distinct phases, a reversible and an irreversible one, which leads to the @entity204 and removal of alveolar cells. Cell @entity204 is preceded by the loss of @entity23117 activity, which abrogates cell differentiation and gain of @entity10433 activity. Despite early observations implicating @entity1379 ( @entity1379 ) family proteins in this process, recent evidence suggests that @entity10433 -controlled cathepsin activity is most critical for cell @entity204 at the early stage of involution. Somewhat surprisingly, this cell @entity204 associates with but does not depend on the activation of pro-apoptotic effector caspases. However, transgenic overexpression of @entity1379 , that blocks caspase activation, delays involution while conditional deletion of @entity26667 accelerates this process, suggesting that @entity1379 family proteins are needed for the effective execution of involution. Here, we report on the transcriptional induction of multiple pro-apoptotic @entity1379 family proteins of the ' @entity2424 -only' subgroup during involution and the rate-limiting role of BIM in this process. Loss of Bim delayed epithelial cell clearance during involution after forced weaning in @entity19 , whereas the absence of related Bmf had minor and loss of @entity30141 or @entity22552 no impact on this process. Consistent with a contribution of @entity1379 family proteins to the second wave of cell @entity204 during involution, loss of Bim reduced the number of apoptotic cells in this irreversible phase. Notably, the expression changes observed within the @entity1379 family did not depend on @entity10433 signalling, in line with its initiating role early in the process, but rather appear to result from relief of repression by @entity23117 . Our findings support the existence of a signalling circuitry regulating the irreversible phase of involution in @entity19 by engaging @entity2424 -only protein-driven mitochondrial apoptosis.

The @entity2424 -only protein BIM contributes to late-stage involution in the XXXX mammary gland.

@entity23117 :: ('20850(Tax:10090)', 'Gene') :: ['STAT5'] @entity19 :: ('10090', 'Species') :: ['mice', 'mouse'] @entity10433 :: ('20848(Tax:10090)', 'Gene') :: ['STAT3'] @entity22552 :: ('58801(Tax:10090)', 'Gene') :: ['Noxa'] @entity30141 :: ('12015(Tax:10090)', 'Gene') :: ['Bad'] @entity1379 :: ('12043(Tax:10090)', 'Gene') :: ['B cell lymphoma 2', 'BCL2'] @entity204 :: ('MESH:D003643', 'Disease') :: ['death'] @entity26667 :: ('12048(Tax:10090)', 'Gene') :: ['BclX'] @entity2424 :: ('MESH:C006008', 'Chemical') :: ['BH3']
@entity19 :: (10090,Species) :: ['mouse']
