GRK2 suppresses lymphomagenesis by inhibiting the MALT1 proto-oncoprotein

Antigen receptor–dependent (AgR-dependent) stimulation of the NF-κB transcription factor in lymphocytes is a required event during adaptive immune response, but dysregulated activation of this signaling pathway can lead to lymphoma. AgR stimulation promotes assembly of the CARMA1-BCL10-MALT1 complex, wherein MALT1 acts as (a) a scaffold to recruit components of the canonical NF-κB machinery, and (b) a protease to cleave and inactivate specific substrates, including negative regulators of NF-κB. In multiple lymphoma subtypes, malignant B cells hijack AgR signaling pathways to promote their own growth and survival, and inhibiting MALT1 reduces the viability and growth of these tumors. As such, MALT1 has emerged as a potential pharmaceutical target. Here, we identified G protein–coupled receptor kinase 2 (GRK2) as a new MALT1-interacting protein. We demonstrated that GRK2 binds the death domain of MALT1 and inhibits MALT1 scaffolding and proteolytic activities. We found that lower GRK2 levels in activated B cell–type diffuse large B cell lymphoma (ABC-DLBCL) are associated with reduced survival, and that GRK2 knockdown enhances ABC-DLBCL tumor growth in vitro and in vivo. Together, our findings suggest that GRK2 can function as a tumor suppressor by inhibiting MALT1 and provide a roadmap for developing new strategies to inhibit MALT1-dependent lymphomagenesis.
Source: Journal of Clinical Investigation - Category: Biomedical Science Authors: Source Type: research

Related Links:

Source: Patient Preference and Adherence - Category: International Medicine & Public Health Tags: Patient Preference and Adherence Source Type: research
Source: OncoTargets and Therapy - Category: Cancer & Oncology Tags: OncoTargets and Therapy Source Type: research
Authors: Meyer D, Smit DP Abstract Both infective and neoplastic eyelid and orbital conditions in human immunodeficiency virus (HIV) infected patients are often the result of opportunistic or co-infections (OI). In most cases, these clinical findings in younger patients alert the physician to suspected underlying HIV infection. When the eyelids and periorbital skin are primarily involved in OI with varicella-zoster virus it is called Herpes Zoster Ophthalmicus. Co-infection with a Pox virus manifests as molluscum contagiosum eruptions. Orbital cellulitis is secondary to various organisms (Mycobacterium tuberculosis...
Source: Ocular Immunology and Inflammation - Category: Allergy & Immunology Tags: Ocul Immunol Inflamm Source Type: research
Authors: Mercuri SR, Paolino G, Colombo L, Bearzi P, Bellinzona F, Perrone S, Sassone M, Berti E, Rizzo N PMID: 32057216 [PubMed - as supplied by publisher]
Source: Giornale Italiano di Dermatologia e Venereologia - Category: Dermatology Tags: G Ital Dermatol Venereol Source Type: research
CONCLUSION: miR-21 and miR-155 promote the progression of Burkitt's lymphoma through PI3K/AKT signaling by targeting C1RL and TCAP. Our findings will provide a novel biomarker and therapeutic strategies for Burkitt's lymphoma. PMID: 32055277 [PubMed]
Source: International Journal of Clinical and Experimental Pathology - Category: Pathology Authors: Tags: Int J Clin Exp Pathol Source Type: research
CONCLUSIONS: This is the first report on discordant lymphoma consisting of mantle cell lymphoma and angioimmunoblastic T cell lymphoma. There seems to be no relation these two different kinds of lymphoma, and EBV infection might prompt the development of angioimmunoblastic T cell lymphoma after transplantation. Rash is a common clinical manifestation when T cell lymphoma develops after treatment for MCL. PMID: 32055275 [PubMed]
Source: International Journal of Clinical and Experimental Pathology - Category: Pathology Authors: Tags: Int J Clin Exp Pathol Source Type: research
In this study, we chose Cytokeratin-pan, GFAP, and LCA as three immunohistochemical indicators. Intraoperative IHC was done by Novodiax ihcDirect technology combined with Leica Bond auto-staining. Compared with the manual method recommended for the reagents (Novodiax ihcDirect), the results show that auto-staining has better stability and high reproducibility in coloration, which has broad prospects for future application. PMID: 32055271 [PubMed]
Source: International Journal of Clinical and Experimental Pathology - Category: Pathology Authors: Tags: Int J Clin Exp Pathol Source Type: research
Publication date: Available online 15 February 2020Source: Clinical Lymphoma Myeloma and LeukemiaAuthor(s): Alan Burnett, Richard StoneAbstractDespite the approval of 8 new drugs for AML since 2017, the disease remains challenging given the significant toxicity associated with available treatments and relatively low cure rates, especially in older adults. While advantageous for patients, self-congratulatory rejoicing about the new agents would be extremely premature. Questions abound about the need for a specific vs less specific FLT3 inhibitor (e.g midostautin) in the upfront setting and whether a single agent (gilteritni...
Source: Clinical Lymphoma Myeloma and Leukemia - Category: Cancer & Oncology Source Type: research
Publication date: Available online 14 February 2020Source: Clinical Lymphoma Myeloma and LeukemiaAuthor(s):
Source: Clinical Lymphoma Myeloma and Leukemia - Category: Cancer & Oncology Source Type: research
In this study, we conducted a comprehensive analysis of the systemic levels of selected growth factors - hepatocyte, vascular-endothelial, fibroblast, and insulin-like 1 growth factors (HGF, VEGF, FGF, and IGF-1, respectively), as well as granulocyte-colony stimulating factor (G-CSF) in 75 patients with different gastric neoplasms (carcinomas, gastrointestinal stromal tumors - GISTs, neuroendocrine neoplasms - NENs, and lymphomas) and 40 healthy volunteers. Patients with gastric carcinoma or other types of gastric neoplasms had higher HGF and IGF-1 levels than healthy individuals (P
Source: American Journal of Translational Research - Category: Research Tags: Am J Transl Res Source Type: research
More News: Biomedical Science | Cancer & Oncology | Lymphoma