Abstract:
Caspase-3 (CASP3) and caspase-7 (CASP7) are the two major executioner caspases that are proteolytically activated by upstream initiator caspases. They possess almost indistinguishable activity, which has led to the overall view that these caspases have functionally redundant roles. Here, we generate knock-in mice expressing cleavage-resistant CASP3(D175A) or CASP7(D198A). Our results show that proteolytic activation of CASP3 and CASP7 is decisive for their activity in vivo and controls redundant processes during embryonic development as combined expression of both CASP3(D175A) and CASP7(D198A) causes embryonic lethality. In adult mice, however, activation of CASP3 and CASP7 controls different processes in different tissues, without the involvement of apoptosis. While CASP7 activation is required for male fertility by controlling spermatogenesis, CASP3 activation appears crucial for lymphoid tissue development by regulating interferon signalling. Our findings shed light on emerging roles of caspases in non-apoptotic processes and provide impetus for reconsidering their involvement in physiological and pathological conditions.
This work is also a wonderful example of how CRC 1530 supports scientific careers. Alongside Noëlle’s development as a clinician scientist, the publication is co-led by senior CRC1530 PI Hamid Kashkar and Melanie Fritsch, who has progressed within the consortium and now joins the CRC as a PI in the second funding period.
Read the full article:
https://link.springer.com/article/10.1038/s44318-026-00871-4
