A novel proteolytic cleavage of ROCK 1 in cell death: Not only by caspases 3 and 7 but also by caspase 2

• Published in: Biochemical and biophysical research communications 2021-04, Vol.547, p.118-124
• Main Authors: Özdemir, Aysun, İbişoğlu, Burçin, Şimay Demir, Yaprak Dilber, Benhür, Elifnur, Valipour, Farzaneh, Ark, Mustafa
• Format: Article
• Language: English
• Subjects: Apoptosis; Caspase 2; Cell death; MCF-7; ROCK 1 cleavage
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2021.02.024

During 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. [Display omitted] •Caspase 2 cleaves ROCK 1 generating an active, approximately 130 kDa, fragment.•Caspase 2-mediated cleavage might occur at the same site where caspase 3 truncates ROCK 1.•The caspase-cleaved product is present in the nuclei and cytoplasm.•A novel ROCK 1 activation mechanism by caspase 2 is defined.