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The role of ARRB2 in the pathogenesis of multiple myeloma (MM) has not been elucidated. This study addressed this question by evaluating the expression of ARRB2 in bone marrow (BM) samples from newly diagnosed MM patients and deriving correlations with key clinical outcomes. In light of recent trends towards the use of immune checkpoint inhibitors across malignancies, the effect of ARRB2 in the regulation of the PD-1\/PD-L1 axis was also investigated. The expression of ARRB2 was significantly higher in MM patients resistant to proteosome inhibitor (bortezomib) treatment compared to those who responded. Higher ARRB2 expression in the BM of newly diagnosed MM patients was associated with inferior progression-free survival and overall survival. PD-1 expression was downregulated in CD3 T cells isolated from ARRB2 knockout (KO) mice. Furthermore, knockdown of ARRB2 with siRNA reduced PD-1 expression in murine CD3 T cells and PD-L1 expression in murine myeloid-derived suppressor cells. These findings suggest an important role of ARRB2 in MM pathogenesis, potentially mediated via modulation of immune checkpoints in the tumor microenvironment. Our study provides new evidence that ARRB2 may have non-canonical functions independent of GPCRs with relevance to the understanding of MM pathobiology as well as immunotherapy and checkpoint inhibitor escape\/resistance more broadly.<\/jats:p>","DOI":"10.3390\/cells14070496","type":"journal-article","created":{"date-parts":[[2025,3,26]],"date-time":"2025-03-26T09:13:26Z","timestamp":1742980406000},"page":"496","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["\u03b2-Arrestin 2 as a Prognostic Indicator and Immunomodulatory Factor in Multiple Myeloma"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2725-3812","authenticated-orcid":false,"given":"Parker","family":"Mathews","sequence":"first","affiliation":[{"name":"Division of Hematologic Malignancies and Cellular Therapy, Department of Medicine, School of Medicine, Duke University Medical Center, Durham, NC 27710, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaobei","family":"Wang","sequence":"additional","affiliation":[{"name":"Division of Hematologic Malignancies and Cellular Therapy, Department of Medicine, School of Medicine, Duke University Medical Center, Durham, NC 27710, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7065-9917","authenticated-orcid":false,"given":"Jian","family":"Wu","sequence":"additional","affiliation":[{"name":"Division of Hematologic Malignancies and Cellular Therapy, Department of Medicine, School of Medicine, Duke University Medical Center, Durham, NC 27710, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shaima","family":"Jabbar","sequence":"additional","affiliation":[{"name":"Division of Hematologic Malignancies and Cellular Therapy, Department of Medicine, School of Medicine, Duke University Medical Center, Durham, NC 27710, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kimberly","family":"Burcher","sequence":"additional","affiliation":[{"name":"Division of Hematologic Malignancies and Cellular Therapy, Department of Medicine, School of Medicine, Duke University Medical Center, Durham, NC 27710, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lindsay","family":"Rein","sequence":"additional","affiliation":[{"name":"Division of Hematologic Malignancies and Cellular Therapy, Department of Medicine, School of Medicine, Duke University Medical Center, Durham, NC 27710, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yubin","family":"Kang","sequence":"additional","affiliation":[{"name":"Division of Hematologic Malignancies and Cellular Therapy, Department of Medicine, School of Medicine, Duke University Medical Center, Durham, NC 27710, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,3,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Cytryn, R., Bickell, N., Yagnik, R., Jagannath, S., and Lin, J.J. (2023). What Affects Treatment Underuse in Multiple Myeloma in the United States: A Qualitative Study. Cancers, 15.","DOI":"10.3390\/cancers15082369"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"108007","DOI":"10.1016\/j.pharmthera.2021.108007","article-title":"Chimeric antigen receptor (CAR) T-cell therapy for multiple myeloma","volume":"232","author":"Choi","year":"2022","journal-title":"Pharmacol. Ther."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1016\/j.clml.2022.12.014","article-title":"SOHO State of the Art Updates and Next Questions: Novel Therapeutic Strategies in Development for Myelofibrosis","volume":"23","author":"Chifotides","year":"2023","journal-title":"Clin. Lymphoma Myeloma Leuk."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"103964","DOI":"10.1016\/j.cellimm.2019.103964","article-title":"The promise of chimeric antigen receptor (CAR) T cell therapy in multiple myeloma","volume":"345","author":"Feinberg","year":"2019","journal-title":"Cell Immunol."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Habrowska-G\u00f3rczy\u0144ska, D.E., Kozie\u0142, M.J., Kowalska, K., and Piastowska-Ciesielska, A.W. (2021). FOXO3a and Its Regulators in Prostate Cancer. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms222212530"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Botticelli, E., Salazar Intriago, M.S., Piovesana, R., and Tata, A.M. (2022). Analysis of Signal Transduction Pathways Downstream M2 Receptor Activation: Effects on Schwann Cell Migration and Morphology. Life, 12.","DOI":"10.3390\/life12020211"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"SD, A., Pasumarthi, D., Pasha, A., Doneti, R., Botlagunta, M., and Pawar, S.C. (2021). Identification of Differentially Expressed Genes in Cervical Cancer Patients by Comparative Transcriptome Analysis. Biomed. Res. Int., 2021.","DOI":"10.1155\/2021\/8810074"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1038\/cr.2012.167","article-title":"beta-arrestin1 regulates gamma-secretase complex assembly and modulates amyloid-beta pathology","volume":"23","author":"Liu","year":"2013","journal-title":"Cell Res."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"665","DOI":"10.1038\/nature17154","article-title":"The conformational signature of beta-arrestin2 predicts its trafficking and signalling functions","volume":"531","author":"Lee","year":"2016","journal-title":"Nature"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"4626","DOI":"10.3390\/ijms21134626","article-title":"beta-Arrestin 2 and ERK1\/2 Are Important Mediators Engaged in Close Cooperation between TRPV1 and micro-Opioid Receptors in the Plasma Membrane","volume":"21","author":"Melkes","year":"2020","journal-title":"Int. J. Mol. Sci."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Fletcher-Jones, A., Hildick, K.L., Evans, A.J., Nakamura, Y., Henley, J.M., and Wilkinson, K.A. (2020). Protein Interactors and Trafficking Pathways That Regulate the Cannabinoid Type 1 Receptor (CB1R). Front. Mol. Neurosci., 13.","DOI":"10.3389\/fnmol.2020.00108"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1097\/FJC.0000000000000482","article-title":"G Protein-Coupled Receptor Signaling Through beta-Arrestin-Dependent Mechanisms","volume":"70","author":"Kaur","year":"2017","journal-title":"J. Cardiovasc. Pharmacol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"854","DOI":"10.1016\/j.jacbts.2021.09.006","article-title":"beta-Arrestin-Mediated Angiotensin II Type 1 Receptor Activation Promotes Pulmonary Vascular Remodeling in Pulmonary Hypertension","volume":"6","author":"Ma","year":"2021","journal-title":"JACC Basic Transl. Sci."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Czogalla, B., Partenheimer, A., Jeschke, U., von Sch\u00f6nfeldt, V., Mayr, D., Mahner, S., Burges, A., Simoni, M., Melli, B., and Benevelli, R. (2020). beta-arrestin 2 Is a Prognostic Factor for Survival of Ovarian Cancer Patients Upregulating Cell Proliferation. Front. Endocrinol., 11.","DOI":"10.3389\/fendo.2020.554733"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1724","DOI":"10.12659\/MSM.905642","article-title":"beta-Arrestin 1\/2 Aggravates Podocyte Apoptosis of Diabetic Nephropathy via Wnt\/beta-Catenin Pathway","volume":"24","author":"Wang","year":"2018","journal-title":"Med. Sci. Monit."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"605","DOI":"10.1074\/jbc.M115.655829","article-title":"beta-Arrestin 2 Promotes Hepatocyte Apoptosis by Inhibiting Akt Protein","volume":"291","author":"Yin","year":"2016","journal-title":"J. Biol. Chem."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"2246","DOI":"10.1016\/j.bbadis.2019.04.020","article-title":"CXCR7 contributes to the aggressive phenotype of cholangiocarcinoma cells. Biochim","volume":"1865","author":"Gentilini","year":"2019","journal-title":"Biophys. Acta Mol. Basis Dis."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1186\/1479-5876-12-6","article-title":"Proteomic profiling of lymphocytes in autoimmunity, inflammation and cancer","volume":"12","author":"Zhou","year":"2014","journal-title":"J. Transl. Med."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Watari, K., Nakaya, M., Nishida, M., Kim, K.-M., and Kurose, H. (2013). beta-arrestin2 in infiltrated macrophages inhibits excessive inflammation after myocardial infarction. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0068351"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"6000","DOI":"10.1038\/s41467-020-19849-9","article-title":"beta-arrestin 2 as an activator of cGAS-STING signaling and target of viral immune evasion","volume":"11","author":"Zhang","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"2806","DOI":"10.1073\/pnas.0807158106","article-title":"Beta-arrestin links endothelin A receptor to beta-catenin signaling to induce ovarian cancer cell invasion and metastasis","volume":"106","author":"Cianfrocca","year":"2009","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Masannat, J., Purayil, H.T., Zhang, Y., Russin, M., Mahmud, I., Kim, W., Liao, D., and Daaka, Y. (2018). \u03b2Arrestin2 Mediates Renal Cell Carcinoma Tumor Growth. Sci. Rep., 8.","DOI":"10.1038\/s41598-018-23212-w"},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Sun, W.-Y., Hu, S.-S., Wu, J.-J., Huang, Q., Ma, Y., Wang, Q.-T., Chen, J.-Y., and Wei, W. (2016). Down-regulation of \u03b2-arrestin2 promotes tumour invasion and indicates poor prognosis of hepatocellular carcinoma. Sci. Rep., 6.","DOI":"10.1038\/srep35609"},{"key":"ref_24","first-page":"631","article-title":"The role and mechanism of beta-arrestins in cancer invasion and metastasis (Review)","volume":"41","author":"Song","year":"2018","journal-title":"Int. J. Mol. Med."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"17591","DOI":"10.1073\/pnas.1209411109","article-title":"Glucocorticoids regulate arrestin gene expression and redirect the signaling profile of G protein-coupled receptors","volume":"109","author":"Oakley","year":"2012","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Shintani, Y., Hayata-Takano, A., Moriguchi, K., Nakazawa, T., Ago, Y., Kasai, A., Seiriki, K., Shintani, N., and Hashimoto, H. (2018). beta-Arrestin1 and 2 differentially regulate PACAP-induced PAC1 receptor signaling and trafficking. PLoS ONE, 13.","DOI":"10.1371\/journal.pone.0196946"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"e98094","DOI":"10.1172\/jci.insight.98094","article-title":"beta-Arrestin2 mediates progression of murine primary myelofibrosis","volume":"2","author":"Rein","year":"2017","journal-title":"JCI Insight"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1016\/j.cellimm.2018.10.003","article-title":"The challenges of checkpoint inhibition in the treatment of multiple myeloma","volume":"334","author":"Paul","year":"2018","journal-title":"Cell Immunol."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Liu, D., Wen, C., Chen, L., Ye, M., Liu, H., Sun, X., Liang, L., Zhang, J., Chang, S., and Liu, J. (2024). The emerging roles of PD-L1 subcellular localization in tumor immune evasion. Biochem. Pharmacol., 220.","DOI":"10.1016\/j.bcp.2023.115984"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"765","DOI":"10.1093\/intimm\/8.5.765","article-title":"Expression of the PD-1 antigen on the surface of stimulated mouse T and B lymphocytes","volume":"8","author":"Agata","year":"1996","journal-title":"Int. Immunol."},{"key":"ref_31","unstructured":"Dammacco, F., and Silvestris, F. (2019). Chapter 38\u2014Emerging Immunotherapies for Renal Cell Carcinoma. Oncogenomics, Academic Press."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"11577","DOI":"10.1200\/JCO.2017.35.15_suppl.11577","article-title":"Function and expression of checkpoint inhibitors and immune agonists on immune cells in monoclonal gammopathy of undetermined significance (MGUS), smoldering multiple myeloma (SMM) and MM and tumor-specific T lymphocytes","volume":"35","author":"Bae","year":"2017","journal-title":"J. Clin. Oncol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"464","DOI":"10.1038\/leu.2012.213","article-title":"Marrow stromal cells induce B7-H1 expression on myeloma cells, generating aggressive characteristics in multiple myeloma","volume":"27","author":"Tamura","year":"2013","journal-title":"Leukemia"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1038\/nrclinonc.2013.208","article-title":"Breathing new life into immunotherapy: Review of melanoma, lung and kidney cancer","volume":"11","author":"Drake","year":"2014","journal-title":"Nat. Rev. Clin. Oncol."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Menon, S., Shin, S., and Dy, G. (2016). Advances in Cancer Immunotherapy in Solid Tumors. Cancers, 8.","DOI":"10.3390\/cancers8120106"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"3335","DOI":"10.1172\/JCI83871","article-title":"Cancer immunotherapy: Harnessing the immune system to battle cancer","volume":"125","author":"Yang","year":"2015","journal-title":"J. Clin. Investig."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"2125","DOI":"10.1200\/JCO.2016.72.1316","article-title":"Phase II Study of the Efficacy and Safety of Pembrolizumab for Relapsed\/Refractory Classic Hodgkin Lymphoma","volume":"35","author":"Chen","year":"2017","journal-title":"J. Clin. Oncol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"2698","DOI":"10.1200\/JCO.2015.65.9789","article-title":"Nivolumab in Patients With Relapsed or Refractory Hematologic Malignancy: Preliminary Results of a Phase Ib Study","volume":"34","author":"Lesokhin","year":"2016","journal-title":"J. Clin. Oncol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"8021","DOI":"10.1200\/JCO.2018.36.15_suppl.8021","article-title":"A phase 3 randomized study of pembrolizumab (Pembro) plus pomalidomide (Pom) and dexamethasone (Dex) for relapsed\/refractory multiple myeloma (RRMM): KEYNOTE-183","volume":"36","author":"Mateos","year":"2018","journal-title":"J. Clin. Oncol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1038\/leu.2008.291","article-title":"Criteria for diagnosis, staging, risk stratification and response assessment of multiple myeloma","volume":"23","author":"Kyle","year":"2009","journal-title":"Leukemia"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"e328","DOI":"10.1016\/S1470-2045(16)30206-6","article-title":"International Myeloma Working Group consensus criteria for response and minimal residual disease assessment in multiple myeloma","volume":"17","author":"Kumar","year":"2016","journal-title":"Lancet Oncol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"3412","DOI":"10.1200\/JCO.2005.04.242","article-title":"International staging system for multiple myeloma","volume":"23","author":"Greipp","year":"2005","journal-title":"J. Clin. Oncol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"4696","DOI":"10.1182\/blood-2010-10-300970","article-title":"Consensus recommendations for risk stratification in multiple myeloma: Report of the International Myeloma Workshop Consensus Panel 2","volume":"117","author":"Munshi","year":"2011","journal-title":"Blood"},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Bond, R.A., Garcia-Rojas, E.Y.L., Hegde, A., and Walker, J.K.L. (2019). Therapeutic Potential of Targeting ss-Arrestin. Front. Pharmacol., 10.","DOI":"10.3389\/fphar.2019.00124"},{"key":"ref_45","first-page":"1601","article-title":"beta-Arrestin 1 and 2 differentially regulate heptahelical receptor signaling and trafficking","volume":"98","author":"Kohout","year":"2001","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"109883","DOI":"10.1016\/j.celrep.2021.109883","article-title":"\u03b22-adrenergic receptor signaling regulates metabolic pathways critical to myeloid-derived suppressor cell function within the TME","volume":"37","author":"Mohammadpour","year":"2021","journal-title":"Cell Rep."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"3177","DOI":"10.1182\/blood-2006-09-044974","article-title":"Gene expression profiling and correlation with outcome in clinical trials of the proteasome inhibitor bortezomib","volume":"109","author":"Mulligan","year":"2007","journal-title":"Blood"},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Wu, L., Jiang, C., Zhu, Z., Sun, Y., and Zhang, T. (2022). Prognostic role of PD-L1 expression in patients with salivary gland carcinoma: A systematic review and meta-analysis. PLoS ONE, 17.","DOI":"10.1371\/journal.pone.0272080"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"3223","DOI":"10.1111\/1759-7714.13650","article-title":"Serum immune modulators during the first cycle of anti-PD-1 antibody therapy in non-small cell lung cancer: Perforin as a biomarker","volume":"11","author":"Ota","year":"2020","journal-title":"Thorac. Cancer"},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Yang, Y., Li, C., Liu, T., Dai, X., and Bazhin, A.V. (2020). Myeloid-Derived Suppressor Cells in Tumors: From Mechanisms to Antigen Specificity and Microenvironmental Regulation. Front. Immunol., 11.","DOI":"10.3389\/fimmu.2020.01371"},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Singh, S., Barik, D., Arukha, A.P., Prasad, S., Mohapatra, I., Singh, A., and Singh, G. (2023). Small Molecule Targeting Immune Cells: A Novel Approach for Cancer Treatment. Biomedicines, 11.","DOI":"10.3390\/biomedicines11102621"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"362","DOI":"10.1038\/s41392-021-00670-9","article-title":"Myeloid-derived suppressor cells as immunosuppressive regulators and therapeutic targets in cancer","volume":"6","author":"Li","year":"2021","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Li, Y., He, H., Jihu, R., Zhou, J., Zeng, R., and Yan, H. (2021). Novel Characterization of Myeloid-Derived Suppressor Cells in Tumor Microenvironment. Front. Cell Dev. Biol., 9.","DOI":"10.3389\/fcell.2021.698532"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"eabb0130","DOI":"10.1126\/scitranslmed.abb0130","article-title":"Radiotherapy and immunotherapy converge on elimination of tumor-promoting erythroid progenitor cells through adaptive immunity","volume":"13","author":"Hou","year":"2021","journal-title":"Sci. Transl. Med."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"854","DOI":"10.1124\/pharmrev.121.000302","article-title":"beta-Arrestins: Structure, Function, Physiology, and Pharmacological Perspectives","volume":"75","author":"Wess","year":"2023","journal-title":"Pharmacol. Rev."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"69641","DOI":"10.18632\/oncotarget.18751","article-title":"A potential panel of two-long non-coding RNA signature to predict recurrence of patients with laryngeal cancer","volume":"8","author":"Bai","year":"2017","journal-title":"Oncotarget"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"100560","DOI":"10.1016\/j.xgen.2024.100560","article-title":"Exploring GPCR signaling pathway networks as cancer therapeutic targets","volume":"4","author":"Santhanam","year":"2024","journal-title":"Cell Genom."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1186\/s12964-023-01170-9","article-title":"The emerging roles of MAPK-AMPK in ferroptosis regulatory network","volume":"21","author":"Wang","year":"2023","journal-title":"Cell Commun. Signal."},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Rochette, L., Dogon, G., Zeller, M., Cottin, Y., and Vergely, C. (2023). Antitumoral Activity of Molecular Hydrogen and Proton in the Treatment of Glioblastoma: An Atypical Pharmacology?. Brain. Sci., 13.","DOI":"10.3390\/brainsci13081168"},{"key":"ref_60","first-page":"407","article-title":"The Effect of Beta-Arrestin2 Overexpression Regarding Viability and Temozolomide Treatment in High-Grade Glioma Cells","volume":"48","author":"Oprita","year":"2022","journal-title":"Curr. Health Sci. J."},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Wojciech, L., Tan, K.S.W., and Gascoigne, N.R.J. (2020). Taming the Sentinels: Microbiome-Derived Metabolites and Polarization of T Cells. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21207740"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1038\/s12276-023-01144-4","article-title":"The multifaceted functions of \u03b2-arrestins and their therapeutic potential in neurodegenerative diseases","volume":"56","author":"Kee","year":"2024","journal-title":"Exp. Mol. Med."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"9790","DOI":"10.1074\/jbc.M112.438804","article-title":"Distinct roles of \u03b2-arrestin 1 and \u03b2-arrestin 2 in ORG27569-induced biased signaling and internalization of the cannabinoid receptor 1 (CB1)","volume":"288","author":"Ahn","year":"2013","journal-title":"J. Biol. Chem."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"5638","DOI":"10.1038\/s41467-022-33307-8","article-title":"\u03b2-arrestin1 and 2 exhibit distinct phosphorylation-dependent conformations when coupling to the same GPCR in living cells","volume":"13","author":"Haider","year":"2022","journal-title":"Nat. Commun."},{"key":"ref_65","doi-asserted-by":"crossref","unstructured":"Wess, J. (2022). The Two \u03b2-Arrestins Regulate Distinct Metabolic Processes: Studies with Novel Mutant Mouse Models. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23010495"},{"key":"ref_66","doi-asserted-by":"crossref","unstructured":"Gurevich, V.V., and Gurevich, E.V. (2019). GPCR Signaling Regulation: The Role of GRKs and Arrestins. Front. Pharmacol., 10.","DOI":"10.3389\/fphar.2019.00125"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"1311","DOI":"10.1056\/NEJMoa1611750","article-title":"Lenalidomide, Bortezomib, and Dexamethasone with Transplantation for Myeloma","volume":"376","author":"Attal","year":"2017","journal-title":"N. Engl. J. Med."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1056\/NEJMoa2204925","article-title":"Triplet Therapy, Transplantation, and Maintenance until Progression in Myeloma","volume":"387","author":"Richardson","year":"2022","journal-title":"N. Engl. J. Med."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1186\/s12943-024-02023-w","article-title":"Regulatory mechanisms of PD-1\/PD-L1 in cancers","volume":"23","author":"Lin","year":"2024","journal-title":"Mol. Cancer"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1016\/j.molcel.2019.09.030","article-title":"Mechanisms Controlling PD-L1 Expression in Cancer","volume":"76","author":"Cha","year":"2019","journal-title":"Mol. Cell"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"643","DOI":"10.1016\/j.molcel.2006.11.007","article-title":"New Roles for \u03b2-Arrestins in Cell Signaling: Not Just for Seven-Transmembrane Receptors","volume":"24","author":"Lefkowitz","year":"2006","journal-title":"Mol. Cell"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1016\/j.tibs.2011.06.003","article-title":"Emerging paradigms of \u03b2-arrestin-dependent seven transmembrane receptor signaling","volume":"36","author":"Shukla","year":"2011","journal-title":"Trends Biochem. Sci."},{"key":"ref_73","doi-asserted-by":"crossref","unstructured":"Szenasi, T., Turu, G., and Hunyady, L. (2023). Interactions between beta-arrestin proteins and the cytoskeletal system, and their relevance to neurodegenerative disorders. Front. Endocrinol., 14.","DOI":"10.3389\/fendo.2023.957981"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1016\/j.addr.2018.07.003","article-title":"Aptamers: Uptake mechanisms and intracellular applications","volume":"134","author":"Yoon","year":"2018","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"10597","DOI":"10.2147\/OTT.S223946","article-title":"Nucleic Acid Aptamer: A Novel Potential Diagnostic and Therapeutic Tool for Leukemia","volume":"12","author":"Tan","year":"2019","journal-title":"Onco Targets Ther."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1186\/s13550-018-0428-y","article-title":"The tetraamine chelator outperforms HYNIC in a new technetium-99m-labelled somatostatin receptor 2 antagonist","volume":"8","author":"Abiraj","year":"2018","journal-title":"EJNMMI Res."}],"container-title":["Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4409\/14\/7\/496\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T17:00:39Z","timestamp":1760029239000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4409\/14\/7\/496"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,3,26]]},"references-count":76,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2025,4]]}},"alternative-id":["cells14070496"],"URL":"https:\/\/doi.org\/10.3390\/cells14070496","relation":{},"ISSN":["2073-4409"],"issn-type":[{"value":"2073-4409","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,3,26]]}}}