Aysun Özdemir, Burçin İbişoğlu, Yaprak Dilber Şimay Demir, Elifnur Benhür, Farzaneh Valipour, Mustafa Ark
Biochemical and biophysical research communications 2021 Apr 02During apoptosis, myosin light chain phosphorylation induced by ROCK 1, activated by caspase 3-mediated cleavage, results in the formation of membrane blebs. Additionally, actin-myosin-based contraction induced by the activation of ROCK is involved in the apoptotic nuclear disintegration. In previous studies, it was reported that ROCK 1 was only cleaved by caspase 3 in cell death and caspase 7 was involved in truncation of ROCK 1 in in-vitro cell-free conditions. Here we reported that caspase 2 is involved in the truncation of ROCK 1 directly as well as caspase 3 and caspase 7. Utilizing caspase 3-deficient MCF-7, MDA-MB-231 and HeLa cells, we demonstrated that caspase 2 produced an active fragment of approximately 130 kDa of ROCK 1 in cell death. The cleaved active fragment of ROCK 1 is also responsible for the formation of membrane blebbing in cell death. Interestingly, caspase 2-mediated cleavage of ROCK 1 might occur in the region where caspase 3 truncates ROCK 1. Moreover, the presence of an active cleaved form of ROCK 1 in the nuclei implies that this fragment might play a role in the disruption of nuclear integrity. Taken together, it was determined that caspase 2 has a role in the truncation of ROCK 1 in cell death, and a new activation mechanism has been defined for ROCK 1. Copyright © 2021 Elsevier Inc. All rights reserved.
Aysun Özdemir, Burçin İbişoğlu, Yaprak Dilber Şimay Demir, Elifnur Benhür, Farzaneh Valipour, Mustafa Ark. A novel proteolytic cleavage of ROCK 1 in cell death: Not only by caspases 3 and 7 but also by caspase 2. Biochemical and biophysical research communications. 2021 Apr 02;547:118-124
PMID: 33610039
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