Genomes and Genes
Summary: Compounds that inhibit the function or proteolytic action of the PROTEASOME.
- Bullova P, Cougnoux A, Marzouca G, Kopacek J, Pacak K. Bortezomib Alone and in Combination With Salinosporamid A Induces Apoptosis and Promotes Pheochromocytoma Cell Death In Vitro and in Female Nude Mice. Endocrinology. 2017;158:3097-3108 pubmed publisherb>Proteasome inhibitors have been frequently used in treating hematologic and solid tumors. They are administered individually or in combination with other regimens, to prevent severe side effects and resistance development...
- Hasinoff B, Patel D. Disulfiram is a slow-binding partial noncompetitive inhibitor of 20S proteasome activity. Arch Biochem Biophys. 2017;633:23-28 pubmed publisher..Disulfiram, which is known to have a high affinity for protein thiols, likely reacted with a non-critical cysteine residue, and not at the proteasome substrate binding site. ..
- Wilck N, Fechner M, Dan C, Stangl V, Stangl K, Ludwig A. The Effect of Low-Dose Proteasome Inhibition on Pre-Existing Atherosclerosis in LDL Receptor-Deficient Mice. Int J Mol Sci. 2017;18: pubmed publisher..Taking recent studies on favorable effects of proteasome inhibition in early atherogenesis into consideration, our data support the hypothesis of stage-dependent effects of proteasome inhibition in atherosclerosis. ..
- McConkey D. The integrated stress response and proteotoxicity in cancer therapy. Biochem Biophys Res Commun. 2017;482:450-453 pubmed publisher..these mechanisms and discusses how the inter-tumor heterogeneity that involves them affects sensitivity and resistance to proteasome inhibitors, a new class of cancer therapeutics that promotes tumor cell killing via proteotoxic stress.
- Leestemaker Y, de Jong A, Witting K, Penning R, Schuurman K, Rodenko B, et al. Proteasome Activation by Small Molecules. Cell Chem Biol. 2017;24:725-736.e7 pubmed publisher..These findings highlight the potential of activation of 26S proteasome activity and that this can be achieved through multiple mechanisms by distinct molecules. ..
- Grosse S, Penaud Budloo M, Herrmann A, BÃ¶rner K, Fakhiri J, Laketa V, et al. Relevance of Assembly-Activating Protein for Adeno-associated Virus Vector Production and Capsid Protein Stability in Mammalian and Insect Cells. J Virol. 2017;91: pubmed publisher..Thereby, our study expands our current understanding of AAV/AAP biology, and it concomitantly provides insights into the importance of AAP for AAV vector production. ..
- Bentea E, Verbruggen L, Massie A. The Proteasome Inhibition Model of Parkinson's Disease. J Parkinsons Dis. 2017;7:31-63 pubmed publisher..findings have inspired the development of a new generation of animal models based on the use of proteasome inhibitors to disturb protein homeostasis and trigger nigral dopaminergic neurodegeneration...
- Genadieva Stavric S, Bonello F, Bringhen S, Boccadoro M, Larocca A. How is patient care for multiple myeloma advancing?. Expert Rev Hematol. 2017;10:551-561 pubmed publisher..are currently available for the treatment of multiple myeloma, including immunomodulatory agents, proteasome inhibitors and autologous stem cell transplantation...
- Blanco B, Palasis K, Adwal A, Callen D, Abell A. Azobenzene-containing photoswitchable proteasome inhibitors with selective activity and cellular toxicity. Bioorg Med Chem. 2017;25:5050-5054 pubmed publisher..Furthermore, cis-enriched 4c inhibited tumor growth in both breast and colorectal carcinoma cell lines. Significantly, the initial trans-enriched TAS of 4c was not cytotoxic against the non-malignant MCF-10A cells. ..
- Oh B, Lee S, Cho H, Park Y, Kim J, Yoon S, et al. Cystatin SN inhibits auranofin-induced cell death by autophagic induction and ROS regulation via glutathione reductase activity in colorectal cancer. Cell Death Dis. 2017;8:e2682 pubmed publisher..These results suggest that high CST1 expression may be involved in autophagic induction and protects from AF-induced cell death by inhibition of ROS generation through the regulation of GR activity. ..
- Mundt S, Basler M, Sawitzki B, Groettrup M. No prolongation of skin allograft survival by immunoproteasome inhibition in mice. Mol Immunol. 2017;88:32-37 pubmed publisher..We conclude that inhibition of the immunoproteasome is not effective in prolonging skin allograft survival in skin allotransplantation. ..
- Lamonte G, Almaliti J, Bibo Verdugo B, Keller L, Zou B, Yang J, et al. Development of a Potent Inhibitor of the Plasmodium Proteasome with Reduced Mammalian Toxicity. J Med Chem. 2017;60:6721-6732 pubmed publisher..This study describes a promising new class of antimalarial compound based on the carmaphycin B scaffold, as well as several chemical structural features that serve to enhance antimalarial specificity. ..
- Yun Z, Zhichao J, Hao Y, Ou J, Ran Y, Wen D, et al. Targeting autophagy in multiple myeloma. Leuk Res. 2017;59:97-104 pubmed publisher..the inhibition of autophagy could effectively induce death in myeloma cells, and could synergize with proteasome inhibitors. However, the excessive activation of autophagy could also lead to the extreme degradation of the ..
- Moreau P, de Wit E. Recent progress in relapsed multiple myeloma therapy: implications for treatment decisions. Br J Haematol. 2017;179:198-218 pubmed publisher..We consider data supporting the addition of the proteasome inhibitors carfilzomib and ixazomib, or the monoclonal antibodies elotuzumab or daratumumab, to a treatment backbone ..
- Park J, Byrd A, Lee C, Morgan E. Nitric oxide stimulates cellular degradation of human CYP51A1, the highly conserved lanosterol 14?-demethylase. Biochem J. 2017;474:3241-3252 pubmed publisher..This down-regulation was partially attenuated by proteasome inhibitors, but only trace levels of ubiquitination could be found...
- Okumura F, Joo Okumura A, Nakatsukasa K, Kamura T. Hypoxia-inducible factor-2? stabilizes the von Hippel-Lindau (VHL) disease suppressor, Myb-related protein 2. PLoS ONE. 2017;12:e0175593 pubmed publisher..These data indicate that oncogenic HIF-2? stabilizes B-Myb to suppress VHL pathogenesis. ..
- Shi D, Smith M, Campbell R, Zimmerman P, Franks Z, Kraemer B, et al. Proteasome function is required for platelet production. J Clin Invest. 2014;124:3757-66 pubmed publisher..These results indicate that proteasome function is critical for thrombopoiesis, and suggest inhibition of RhoA signaling as a potential strategy to treat thrombocytopenia in bortezomib-treated multiple myeloma patients. ..
- Liu R, Zhang P, Yang C, Pang Y, Zhang M, Zhang N, et al. ONX-0914, a selective inhibitor of immunoproteasome, ameliorates experimental autoimmune myasthenia gravis by modulating humoral response. J Neuroimmunol. 2017;311:71-78 pubmed publisher..Also it reduced the percentage of Th17 cells and inhibited the secretion of IL-17. Our data indicated ONX-0914 may bring benefit for MG therapy. ..
- Maehama T, Kawahara K, Nishio M, Suzuki A, Hanada K. Nucleolar stress induces ubiquitination-independent proteasomal degradation of PICT1 protein. J Biol Chem. 2014;289:20802-12 pubmed..The proteasome inhibitors MG132, lactacystin, and epoxomicin blocked PICT1 degradation, whereas the inhibition of E1 ubiquitin-..
- Weathington N, Mallampalli R. Emerging therapies targeting the ubiquitin proteasome system in cancer. J Clin Invest. 2014;124:6-12 pubmed publisher..In this article, we discuss the biology of UPS-targeting drugs, their use as therapy for neoplasia, and the state of clinical and preclinical development for emerging therapeutics. ..
- Nelson N, Szekeres K, Iclozan C, Rivera I, McGill A, Johnson G, et al. Apigenin: Selective CK2 inhibitor increases Ikaros expression and improves T cell homeostasis and function in murine pancreatic cancer. PLoS ONE. 2017;12:e0170197 pubmed publisher..More importantly, our findings suggest that API may be a possible therapeutic agent for stabilizing Ikaros expression and function to maintain T cell homeostasis in murine PC. ..
- Tsuchiya H, Ohtake F, Arai N, Kaiho A, Yasuda S, Tanaka K, et al. In Vivo Ubiquitin Linkage-type Analysis Reveals that the Cdc48-Rad23/Dsk2 Axis Contributes to K48-Linked Chain Specificity of the Proteasome. Mol Cell. 2017;66:488-502.e7 pubmed publisher..Collectively, our results provide an overall picture of the ubiquitin network via UBD proteins and identify the Cdc48-Rad23/Dsk2 axis as a major route to the proteasome. ..
- Burslem G, Crews C. Small-Molecule Modulation of Protein Homeostasis. Chem Rev. 2017;117:11269-11301 pubmed publisher..In this Review, we discuss the technologies available for the control of intracellular protein levels with small molecules and compare the various systems available. ..
- Marastoni M, Trapella C, Scotti A, Fantinati A, Ferretti V, Marzola E, et al. Naphthoquinone amino acid derivatives, synthesis and biological activity as proteasome inhibitors. J Enzyme Inhib Med Chem. 2017;32:865-877 pubmed publisher..Because of their antitumour activity, different classes of proteasome inhibitors have been identified to date...
- Ao N, Chen Q, Liu G. The Small Molecules Targeting Ubiquitin-Proteasome System for Cancer Therapy. Comb Chem High Throughput Screen. 2017;20:403-413 pubmed publisher..In the present review, we exhibit the crucial ingredients involved in UPS and discuss the current situation of small molecules targeting various components of ubiquitination pathway in cancer treatment. ..
- Yuan B, Chapman J, Ding M, Wang J, Jiang B, Rojanasakul Y, et al. TRAIL and proteasome inhibitors combination induces a robust apoptosis in human malignant pleural mesothelioma cells through Mcl-1 and Akt protein cleavages. BMC Cancer. 2013;13:140 pubmed publisher..b>Proteasome inhibitors (PIs) and TNF?-Related Apoptosis Inducing Ligand (TRAIL), have emerged as promising new anti-MPM agents...
- Suvannasankha A, Chirgwin J. Role of bone-anabolic agents in the treatment of breast cancer bone metastases. Breast Cancer Res. 2014;16:484 pubmed..b>Proteasome inhibitors (bortezomib and carfilzomib) inhibit the growth of myeloma directly and are anabolic for bone...
- Chen Y, Yeh M, Yu M, Wei Y, Chen W, Chen J, et al. Lapatinib-induced NF-kappaB activation sensitizes triple-negative breast cancer cells to proteasome inhibitors. Breast Cancer Res. 2013;15:R108 pubmed publisher..Triple-negative breast cancer cell lines were treated with proteasome inhibitors in combination with lapatinib (a dual epidermal growth factor receptor (EGFR)/HER2 tyrosine kinase ..
- Veltri L, Milton D, Delgado R, Shah N, Patel K, Nieto Y, et al. Outcome of autologous hematopoietic stem cell transplantation in refractory multiple myeloma. Cancer. 2017;123:3568-3575 pubmed publisher..of patients with refractory multiple myeloma remains poor, particularly those who are refractory to both proteasome inhibitors (PIs) and immunomodulatory agents (IMiDs)...
- Sheng X, Tu H, Chien W, Kang K, Lu D, Liou H, et al. Antagonism of proteasome inhibitor-induced heme oxygenase-1 expression by PINK1 mutation. PLoS ONE. 2017;12:e0183076 pubmed publisher..In this study, we demonstrated that the G309D mutation impairs the neuroprotective function of PINK1 following proteasome inhibition, which may be related to the pathogenesis of PD. ..
- D Agostino M, Salvini M, Palumbo A, Larocca A, Gay F. Novel investigational drugs active as single agents in multiple myeloma. Expert Opin Investig Drugs. 2017;26:699-711 pubmed publisher..The drugs discussed include alkylators, new proteasome inhibitors, novel anti-CD38 monoclonal antibodies, Bcl-2 inhibitors, Cyclin-Dependent-Kinase inhibitor, Kinesin-..
- Song Y, Li S, Ray A, Das D, Qi J, Samur M, et al. Blockade of deubiquitylating enzyme Rpn11 triggers apoptosis in multiple myeloma cells and overcomes bortezomib resistance. Oncogene. 2017;36:5631-5638 pubmed publisher..Overall, our preclinical data provide the rationale for targeting DUB enzyme Rpn11 upstream of 20S proteasome to enhance cytotoxicity and overcome proteasome inhibitor resistance in MM...
- Geng C, Kaochar S, Li M, Rajapakshe K, Fiskus W, Dong J, et al. SPOP regulates prostate epithelial cell proliferation and promotes ubiquitination and turnover of c-MYC oncoprotein. Oncogene. 2017;36:4767-4777 pubmed publisher..We propose SPOPMT-induced stabilization of c-MYC protein as a novel mechanism that can increase total c-MYC levels in PC cells, in addition to amplification of c-MYC locus. ..
- Shen K, Li X, Dai X, Wang P, Li S, Xiong Z, et al. Effects of MG132 on the in vitro development and epigenetic modification of Debao porcine somatic cell nuclear transfer embryos. Theriogenology. 2017;94:48-58 pubmed publisher..These results demonstrate that MG132 treatment can improve the developmental potential of Debao porcine SCNT embryos through regulating the expression of genes related to histone acetylation and the processes of ZGA. ..
- Krahn J, Kaschani F, Kaiser M. Turning-ON Proteasomes. Cell Chem Biol. 2017;24:653-655 pubmed publisherWhile proteasome inhibitors are now well-established research tools and chemotherapeutics, proteasome activators are much less explored...
- Kim Y, Cho N, Cheon S, Kim K. Bortezomib, a proteasome inhibitor, alleviates atopic dermatitis by increasing claudin 1 protein expression. Biochem Biophys Res Commun. 2017;493:744-750 pubmed publisher..Taken together, these results demonstrate that BTZ-induced claudin 1 expression may be a valuable therapeutic approach for AD. ..
- Subjeck J, Repasky E. Heat shock proteins and cancer therapy: the trail grows hotter!. Oncotarget. 2011;2:433-4 pubmed
- Baleeiro R, Walden P. Immature human DCs efficiently translocate endocytosed antigens into the cytosol for proteasomal processing. Mol Immunol. 2017;88:148-154 pubmed publisher..b>Proteasome inhibitors reduced the required concentration of cytochrome c thousand-fold, indicating that protein translocated ..
- Podar K, Pecherstorfer M. Current and developing synthetic pharmacotherapy for treating relapsed/refractory multiple myeloma. Expert Opin Pharmacother. 2017;18:1061-1079 pubmed publisher..Areas covered: Proteasome inhibitors, immunomodulatory drugs, and monoclonal antibodies are prototype drug classes, which target both specific ..
- Mazurkiewicz M, Hillert E, Wang X, Pellegrini P, Olofsson M, Selvaraju K, et al. Acute lymphoblastic leukemia cells are sensitive to disturbances in protein homeostasis induced by proteasome deubiquitinase inhibition. Oncotarget. 2017;8:21115-21127 pubmed publisher..We conclude that ALL cells are highly sensitive to the proteasome DUB inhibitor VLX1570 suggesting a novel therapeutic option for this disease. ..
- Sidor Kaczmarek J, Cichorek M, Spodnik J, Wójcik S, Morys J. Proteasome inhibitors against amelanotic melanoma. Cell Biol Toxicol. 2017;33:557-573 pubmed publisher..In this work, we analyze the cytotoxicity mechanisms of proteasome inhibitors (MG-132, epoxomicin, and lactacystin) in a specific form of melanoma which does not synthesize melanin-the ..
- Herrero Álvarez N, van de Langemheen H, Brouwer A, Liskamp R. Potential peptidic proteasome inhibitors by incorporation of an electrophilic trap based on amino acid derived ?-substituted sulfonyl fluorides. Bioorg Med Chem. 2017;25:5055-5063 pubmed publisher..Unfortunately, the poor solubility of the resulting ?PSFs precluded a proper evaluation of their biological activity. ..
- Yi J, Paranjape S, Walker M, Choudhury R, Wolter J, Fragola G, et al. The autism-linked UBE3A T485A mutant E3 ubiquitin ligase activates the Wnt/?-catenin pathway by inhibiting the proteasome. J Biol Chem. 2017;292:12503-12515 pubmed publisher..Our study has broad implications for human disorders associated with UBE3A gain or loss of function and suggests that dysfunctional UBE3A might affect additional proteins and pathways that are sensitive to proteasome activity. ..
- Yue X, Zuo Y, Ke H, Luo J, Lou L, Qin W, et al. Identification of 4-arylidene curcumin analogues as novel proteasome inhibitors for potential anticancer agents targeting 19S regulatory particle associated deubiquitinase. Biochem Pharmacol. 2017;137:29-50 pubmed publisher..These systematic studies provided insights in the development of novel proteasome inhibitors for cancer treatment.