Mardilovich, Katerina and Naylor, Gregory and Julian, Linda and Phinichkusolchit, Narisa and Keeshan, Karen and Blyth, Karen and Olson, Michael F. (2024) Caspase-resistant ROCK1 expression prolongs survival of Eµ-Myc B cell lymphoma mice. Disease Models and Mechanisms, 17 (5): dmm050631. ISSN 1754-8403
AI Summary:
Apoptosis is characterized by membrane blebbing and apoptotic body formation. The study found that caspase-resistant non-cleavable ROCK1 Rock1 NC prolonged survival of mice with B cell lymphomas.AI Topics:
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Apoptosis is characterized by membrane blebbing and apoptotic body formation. Caspase cleavage of ROCK1 generates an active fragment that promotes actin-myosin mediated contraction and membrane blebbing during apoptosis. Expression of caspase-resistant non-cleavable ROCK1 (Rock1 NC) prolonged survival of mice that rapidly develop B cell lymphomas due to Eµ-Myc transgene expression. Eµ-Myc; Rock1 NC mice had significantly fewer bone marrow cells relative to Eµ-Myc mice expressing wild-type ROCK1 (Rock1 WT), which was associated with altered cell cycle profiles. Circulating macrophage numbers were lower in Eµ-Myc; Rock1 NC mice, but there were higher levels of bone marrow macrophages, consistent with spontaneous cell death in Eµ-Myc; Rock1 NC mice bone marrows being more inflammatory. Rock1 WT recipient mice transplanted with pre-neoplastic Eµ-Myc; Rock1 NC bone marrow cells survived longer than mice transplanted with Eµ-Myc; Rock1 WT cells, indicating that the survival benefit was intrinsic to the Eµ-Myc; Rock1 NC bone marrow cells. The results suggest that the apoptotic death of Eµ-Myc; Rock1 NC cells generates a proliferation-suppressive microenvironment in bone marrows that reduces cell numbers and prolongs B cell lymphoma mouse survival.
Title | Caspase-resistant ROCK1 expression prolongs survival of Eµ-Myc B cell lymphoma mice |
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Creators | Mardilovich, Katerina and Naylor, Gregory and Julian, Linda and Phinichkusolchit, Narisa and Keeshan, Karen and Blyth, Karen and Olson, Michael F. |
Identification Number | 10.1242/dmm.050631 |
Date | May 2024 |
Divisions | College of Medical Veterinary and Life Sciences > School of Cancer Sciences |
Publisher | The Company of Biologists Ltd. |
Additional Information | Funding: This study was funded by Cancer Research UK (CRUK) institutional funding to the CRUK Beatson Institute (A10419 and A17196), to the Blyth laboratory (A29799) and to the Olson laboratory (A18276). Additional funding to M.F.O. was from the Canadian Institutes of Health Research (PJT-169125), Natural Sciences and Engineering Research Council of Canada (RGPIN-2020-05388) and the Canada Research Chairs Program (950-231665). Open Access funding provided by Canadian Institutes of Health Research. |
URI | https://pub.demo35.eprints-hosting.org/id/eprint/284 |
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Item Type | Article |
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Depositing User | Unnamed user with email ejo1f20@soton.ac.uk |
SWORD Depositor | Users 37347 not found. |
Date Deposited | 11 Jun 2025 16:36 |
Revision | 19 |
Last Modified | 12 Jun 2025 11:00 |
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