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, cilt.547, ss.118-124, 2021 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 547
  • Basım Tarihi: 2021
  • Doi Numarası: 10.1016/j.bbrc.2021.02.024
  • Dergi Adı: BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, Aquatic Science & Fisheries Abstracts (ASFA), BIOSIS, CAB Abstracts, Chemical Abstracts Core, EMBASE, Food Science & Technology Abstracts, MEDLINE, Veterinary Science Database
  • Sayfa Sayıları: ss.118-124
  • Anahtar Kelimeler: ROCK 1 cleavage, Caspase 2, MCF-7, Cell death, Apoptosis
  • Gazi Üniversitesi Adresli: Evet

Özet

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.