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


Özdemir A. , İbişoğlu B., Şimay Demir Y. D. , Benhür E., Valipour F., Ark M.

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, vol.547, pp.118-124, 2021 (Journal Indexed in SCI) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 547
  • Publication Date: 2021
  • Doi Number: 10.1016/j.bbrc.2021.02.024
  • Title of Journal : BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
  • Page Numbers: pp.118-124

Abstract

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.