cFLIP – An interacting partner and a novel substrate for pro-apoptotic serine protease HtrA2
Biochemistry and Biophysics Reports(2024)
摘要
Background
HtrA2, a pro-apoptotic protease, plays a crucial role in apoptosis by cleaving inhibitory and anti-apoptotic proteins by translocating from mitochondria to the cytosol. Prior studies in ischemic cells have indicated that cytosolic HtrA2 triggers cFLIP degradation, plausibly through direct interaction. In this study, we have characterized the cFLIP protein, validated its interaction with HtrA2, and demonstrated that cFLIP is also a substrate of HtrA2.
Methods
We have identified the probable cleavage sites of cFLIP through gel-based assays and mass spectrometric analysis of the cleaved fragments.
Results
Our findings shed light on a key protein-protein interaction involving pro-apoptotic HtrA2, confirming cFLIP as its interacting partner and substrate.
Conclusion
Understanding the nuances of HtrA2's interaction with cFLIP (a decoy protein of the initiator procaspase-8 in the extrinsic apoptotic pathway) and deciphering the cFLIP's mode of cleavage, would provide an excellent alternative to modulate the pathway for therapeutic benefits toward diseases like ischemia and cancer.
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关键词
cFLIP,HtrA2,Apoptosis,DISC,Ischemia,Cancer
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