The proteasome regulates collagen-induced platelet aggregation via nuclear-factor-kappa-B (NFĸB) activation

Gründler, Katharina; Rotter, Raffaela; Tilley, Sloane K.; Pircher, Joachim; Czermak, Thomas; Yakac, Mustaf; Gaitzsch, Erik; Maßberg, Steffen; Krötz, Florian; Sohn, Hae-Young; Pohl, Ulrich; Mannell, Hanna; Kraemer, Bjoern F.

doi:10.1016/j.thromres.2016.10.009

Cited by 26 publications

(34 citation statements)

References 49 publications

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“…In addition, PA28αβ (PA, proteasome activator) is a regulatory particle which can be attached to the 20S complex. The combination of 19S, 20S, and PA28αβ is called hybrid proteasome…”

Section: Protein Degradation By Proteasome Complexesmentioning

confidence: 99%

“…Proteasome inhibitor treatment resulted in decreased aggregation in response to low concentrations of thrombin (0.025 U/mL) and collagen (1‐2 µg/mL). However, as the experimental conditions varied between the studies, it is too early to draw definite conclusions on underlying mechanisms . In addition to direct interference of the proteasome activity with platelet aggregation, the platelet cytoskeleton proteins Filamin A and Talin‐1 are ubiquitinated and subsequently degraded by proteasomes …”

Section: Impact Of Proteasome Function On Platelet Production and Actmentioning

confidence: 99%

“…Thus, platelet activation is regulated by the ubiquitin‐proteasome system, partially via NF‐κB‐activation . NF‐κB is also a key regulator of inflammation.…”

Section: Identification Of E3 Ubiquitin Ligases In Plateletsmentioning

confidence: 99%

“…A prominent example is the regulation of the nuclear factor kappa‐light‐chain‐enhancer of activated B cells (NF‐κB) pathway originally described in nucleated cells but surprisingly observed in platelets as well. Here activation is accomplished by ubiquitination of the NF‐κB‐inhibitor IκBα and its subsequent degradation by the proteasome complex (Figure ) . The proteasome is also relevant for modulating the signaling pathways of αIIbβ3, GPVI, and CLEC‐2 (Figure ) and might play a pivotal role in additional signaling pathways in platelets .…”

Section: Introductionmentioning

confidence: 99%

“…Here activation is accomplished by ubiquitination of the NF-κB-inhibitor IκBα and its subsequent degradation by the proteasome complex ( Figure 1). [14][15][16] The proteasome is also relevant for modulating the signaling pathways of αIIbβ3, GPVI, and CLEC-2 ( Figure 1) and might play a pivotal role in additional signaling pathways in platelets. [17][18][19][20][21][22] In this review, we summarize the known fundamental regulatory mechanisms and functional aspects of the proteasome in human platelets.…”

mentioning

confidence: 99%

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Structure and function of the ubiquitin‐proteasome system in platelets

Colberg

Cammann

Greinacher

et al. 2020

Journal of Thrombosis and Haemostasis

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Platelets are small anucleate blood cells with a life span of 7 to 10 days. They are main regulators of hemostasis. Balanced platelet activity is crucial to prevent bleeding or occlusive thrombus formation. Growing evidence supports that platelets also participate in immune reactions, and interaction between platelets and leukocytes contributes to both thrombosis and inflammation. The ubiquitin‐proteasome system (UPS) plays a key role in maintaining cellular protein homeostasis by its ability to degrade non‐functional self‐, foreign, or short‐lived regulatory proteins. Platelets express standard and immunoproteasomes. Inhibition of the proteasome impairs platelet production and platelet function. Platelets also express major histocompatibility complex (MHC) class I molecules. Peptide fragments released by proteasomes can bind to MHC class I, which makes it also likely that platelets can activate epitope specific cytotoxic T lymphocytes (CTLs). In this review, we focus on current knowledge on the significance of the proteasome for the functions of platelets as critical regulators of hemostasis as well as modulators of the immune response.

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“…In addition, PA28αβ (PA, proteasome activator) is a regulatory particle which can be attached to the 20S complex. The combination of 19S, 20S, and PA28αβ is called hybrid proteasome…”

Section: Protein Degradation By Proteasome Complexesmentioning

confidence: 99%

Section: Impact Of Proteasome Function On Platelet Production and Actmentioning

confidence: 99%

“…Thus, platelet activation is regulated by the ubiquitin‐proteasome system, partially via NF‐κB‐activation . NF‐κB is also a key regulator of inflammation.…”

Section: Identification Of E3 Ubiquitin Ligases In Plateletsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%