Caspase-activated ROCK-1 allows erythroblast terminal maturation independently of cytokine-induced Rho signaling

Gabet, A-S; Coulon, Séverine; Fricot, Aurélie; Vandekerckhove, Julie; Chang, Yunhua; Ribeil, Jean‐Antoine; Lordier, Larissa; Zermati, Yaël; Asnafi, Vahid; Belaid, Zakia; Debili, Najet; Vainchenker, William; Varet, Bruno; Hermine, Olivier; Courtois, Geneviève

doi:10.1038/cdd.2010.140

Cited by 26 publications

(18 citation statements)

References 39 publications

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“…It is possible that these proteins are also involved in chromatin condensation in erythroid differentiation. In addition, caspase-3 also activates ROCK-1, which allows terminal erythroid differentiation in part through phosphorylation of myosin II light chain (Gabet et al, 2011). How caspase-3 coordinates the cleavage of nuclear membrane proteins with the activation of DNase and ROCK-1 would be interesting to explore.…”

Section: Discussionmentioning

confidence: 99%

Nuclear Condensation during Mouse Erythropoiesis Requires Caspase-3-Mediated Nuclear Opening

et al. 2016

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SUMMARY Mammalian erythropoiesis involves chromatin condensation that is initiated in the early stage of terminal differentiation. The mechanisms of chromatin condensation during erythropoiesis are unclear. Here, we show that the mouse erythroblast forms large, transient, and recurrent nuclear openings that coincide with the condensation process. The opening lacks nuclear lamina, nuclear pore complexes, and nuclear membrane, but it is distinct from nuclear envelope changes that occur during apoptosis and mitosis. A fraction of the major histones are released from the nuclear opening and degraded in the cytoplasm. We demonstrate that caspase-3 is required for the nuclear opening formation throughout terminal erythropoiesis. Loss of caspase-3 or ectopic expression of a caspase-3 non-cleavable lamin B mutant blocks nuclear opening formation, histone release, chromatin condensation, and terminal erythroid differentiation. We conclude that caspase-3-mediated nuclear opening formation accompanied by histone release from the opening is a critical step towards chromatin condensation during erythropoiesis in mice.

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Section: Discussionmentioning

confidence: 99%

Nuclear Condensation during Mouse Erythropoiesis Requires Caspase-3-Mediated Nuclear Opening

et al. 2016

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“…31,32 During the development of erythroblasts, ROCK1 is activated by caspase-3-mediated cleavage, allowing terminal maturation through phosphorylation of the light chain of myosin II. 33 Granzyme B is a serine protease expressed in the granules of cytotoxic lymphocytes, basophils, mast cells, and VSMC. 34 Granzyme B induces inflammation by cytokine release and contributes to the extracellular matrix remodeling.…”

Section: Molecular Roles and Regulation Of Rho-kinase In The Cardiovamentioning

confidence: 99%

RhoA/Rho-Kinase in the Cardiovascular System

Shimokawa

Sunamura

Satoh

2016

Circulation Research

370

235

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Twenty years ago, Rho-kinase was identified as an important downstream effector of the small GTP-binding protein, RhoA. Thereafter, a series of studies demonstrated the important roles of Rho-kinase in the cardiovascular system. The RhoA/Rho-kinase pathway is now widely known to play important roles in many cellular functions, including contraction, motility, proliferation, and apoptosis, and its excessive activity induces oxidative stress and promotes the development of cardiovascular diseases. Furthermore, the important role of Rho-kinase has been demonstrated in the pathogenesis of vasospasm, arteriosclerosis, ischemia/reperfusion injury, hypertension, pulmonary hypertension, and heart failure. Cyclophilin A is secreted by vascular smooth muscle cells and inflammatory cells and activated platelets in a Rho-kinase–dependent manner, playing important roles in a wide range of cardiovascular diseases. Thus, the RhoA/Rho-kinase pathway plays crucial roles under both physiological and pathological conditions and is an important therapeutic target in cardiovascular medicine. Recently, functional differences between ROCK1 and ROCK2 have been reported in vitro. ROCK1 is specifically cleaved by caspase-3, whereas granzyme B cleaves ROCK2. However, limited information is available on the functional differences and interactions between ROCK1 and ROCK2 in the cardiovascular system in vivo. Herein, we will review the recent advances about the importance of RhoA/Rho-kinase in the cardiovascular system.

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“…Recently, Gabet et al demonstrated the involvement of ROCK1 in terminal maturation of erythroid cells using ROCK inhibitors and by knockdown of ROCK1. 34 Although useful, these studies do not distinguish between the physiologic functions of ROCK1 and ROCK2, thereby underscoring the importance of these related family members in regulating different functions. Importantly, the physiologic role of ROCK in blood cells is poorly defined.…”

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confidence: 99%

ROCK1 functions as a critical regulator of stress erythropoiesis and survival by regulating p53

Vemula¹,

Shi²,

Mali³

et al. 2012

Blood

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Erythropoiesis is a dynamic, multistep process whereby hematopoietic stem cells differentiate toward a progressively committed erythroid lineage through intermediate progenitors. Although several downstream signaling molecules have been identified that regulate steady-state erythropoiesis, the major regulators under conditions of stress remain poorly defined. Rho kinases (ROCKs) belong to a family of serine/threonine kinases. Using gene-targeted ROCK1-deficient mice, we show that lack of ROCK1 in phenylhydrazine-induced oxidative stress model results in enhanced recovery from hemolytic anemia as well as enhanced splenic stress erythropoiesis compared with control mice. Deficiency of ROCK1 also results in enhanced survival, whereas wild-type mice die rapidly in response to stress. Enhanced survivability of ROCK1-deficient mice is associated with reduced level of reactive oxygen species. BM transplantation studies revealed that enhanced stress erythropoiesis in ROCK1-deficient mice is stem cell autonomous.We show that ROCK1 binds to p53 and regulates its stability and expression. In the absence of ROCK1, p53 phosphorylation and expression is significantly reduced. Our findings reveal that ROCK1 functions as a physiologic regulator of p53 under conditions of erythroid stress. These findings are expected to offer new perspectives on stress erythropoiesis and may provide a potential therapeutic target in human disease characterized by anemia. (Blood. 2012;120(14):2868-2878) IntroductionErythropoiesis is a multistep process in which multipotential hematopoietic stem cells (HSCs) differentiate toward a progressively committed erythroid lineage through intermediate progenitors, specifically, burst forming units-erythroid (BFU-E), followed sequentially by colony forming units-erythroid (CFU-E), proerythroblasts, erythroblasts, reticulocytes and, finally, enucleated erythrocytes. 1 The regulation of erythropoiesis is stringent and maintained by the combined effects of transcription factors, GATA 1, Fog1 zinc-finger factors, forkhead factor 3a (Foxo3a), and erythroid Krüppel-like factor (Eklf), which are essential for recruitment of hematopoietic stem cells into the erythroid lineage. 2,3 Hormones and cytokines, such as erythropoietin (EPO), stem cell factor (SCF), glucocorticoids, bone morphogenic protein-4 (BMP-4) are important for erythroid cell proliferation, sequential differentiation, maturation, and survival. [4][5][6][7][8] Under normal physiologic conditions, erythropoiesis takes place primarily in the BM of humans and mice. Under erythroid stress conditions in mice, such as anemia or hypoxia, splenic erythropoietic population increases because of BMP4-dependent stress erythropoiesis resulting in extramedullary erythropoiesis. 5,9,10 Efficient erythropoiesis is crucial for the survival and recovery from various pathophysiologic conditions including blood loss, anemia, and therapeutic procedures used in the treatment of hematologic malignancies including chemotherapy and stem cell transplantation. Impaired or defec...

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Caspase-activated ROCK-1 allows erythroblast terminal maturation independently of cytokine-induced Rho signaling

Cited by 26 publications

References 39 publications

Nuclear Condensation during Mouse Erythropoiesis Requires Caspase-3-Mediated Nuclear Opening

Nuclear Condensation during Mouse Erythropoiesis Requires Caspase-3-Mediated Nuclear Opening

RhoA/Rho-Kinase in the Cardiovascular System

ROCK1 functions as a critical regulator of stress erythropoiesis and survival by regulating p53

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