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Proteasom dan subunitnya memiliki signifikansi klinis karena perakitan kompleks yang dikompromikan atau proteasom disfungsional dapat dikaitkan dengan patofisiologi yang mendasari penyakit tertentu, dan proteasom dapat dimanfaatkan sebagai target obat untuk terapi. Baru-baru ini, juga banyak upaya telah dilakukan untuk mempertimbangkan proteasom untuk pengembangan penanda dan strategi diagnostik baru.
 
Proteasom membentuk komponen penting untuk sistem ubiquitin-proteasom (UPS)<ref>{{Cite journal|last=Kleiger|first=Gary|last2=Mayor|first2=Thibault|date=2014-06|title=Perilous journey: a tour of the ubiquitin-proteasome system|url=https://pubmed.ncbi.nlm.nih.gov/24457024|journal=Trends in Cell Biology|volume=24|issue=6|pages=352–359|doi=10.1016/j.tcb.2013.12.003|issn=1879-3088|pmc=4037451|pmid=24457024}}</ref> dan kontrol kualitas protein seluler yang sesuai. Ubiquitinasi protein dan proteolisis dan degradasi selanjutnya oleh proteasom merupakan mekanisme penting dalam regulasi siklus sel, pertumbuhan dan diferensiasi sel, transkripsi gen, transduksi sinyal dan apoptosis.<ref>{{Cite journal|last=Goldberg|first=A. L.|last2=Stein|first2=R.|last3=Adams|first3=J.|date=1995-08|title=New insights into proteasome function: from archaebacteria to drug development|url=https://pubmed.ncbi.nlm.nih.gov/9383453|journal=Chemistry & Biology|volume=2|issue=8|pages=503–508|doi=10.1016/1074-5521(95)90182-5|issn=1074-5521|pmid=9383453}}</ref> Selanjutnya, perakitan dan fungsi kompleks proteasom yang dikompromikan menyebabkan berkurangnya aktivitas proteolitik dan akumulasi spesies protein yang rusak atau salah lipat. Akumulasi protein tersebut dapat berkontribusi pada patogenesis dan karakteristik fenotipik pada penyakit neurodegeneratif,<ref>{{Cite journal|last=Penke|first=Botond|last2=Bogár|first2=Ferenc|last3=Fülöp|first3=Lívia|date=2017-10-10|title=β-Amyloid and the Pathomechanisms of Alzheimer’s Disease: A Comprehensive View|url=http://www.mdpi.com/1420-3049/22/10/1692|journal=Molecules|language=en|volume=22|issue=10|pages=1692|doi=10.3390/molecules22101692|issn=1420-3049|pmc=PMC6151811|pmid=28994715}}</ref><ref>{{Cite journal|last=Ortega|first=Zaira|last2=Lucas|first2=Jose J.|date=2014|title=Ubiquitin-proteasome system involvement in Huntington's disease|url=https://pubmed.ncbi.nlm.nih.gov/25324717|journal=Frontiers in Molecular Neuroscience|volume=7|pages=77|doi=10.3389/fnmol.2014.00077|issn=1662-5099|pmc=4179678|pmid=25324717}}</ref> penyakit kardiovaskular,<ref>{{Cite journal|last=Sandri|first=Marco|last2=Robbins|first2=Jeffrey|date=2014-06|title=Proteotoxicity: an underappreciated pathology in cardiac disease|url=https://pubmed.ncbi.nlm.nih.gov/24380730|journal=Journal of Molecular and Cellular Cardiology|volume=71|pages=3–10|doi=10.1016/j.yjmcc.2013.12.015|issn=1095-8584|pmc=4011959|pmid=24380730}}</ref><ref>{{Cite journal|last=Wang|first=Zhao V.|last2=Hill|first2=Joseph A.|date=2015-02-03|title=Protein quality control and metabolism: bidirectional control in the heart|url=https://pubmed.ncbi.nlm.nih.gov/25651176|journal=Cell Metabolism|volume=21|issue=2|pages=215–226|doi=10.1016/j.cmet.2015.01.016|issn=1932-7420|pmc=4317573|pmid=25651176}}</ref> respons inflamasi dan penyakit autoimun,<ref name=Hoesel>{{Cite journal|last=Hoesel|first=Bastian|last2=Schmid|first2=Johannes A|date=2013|title=The complexity of NF-κB signaling in inflammation and cancer|url=http://molecular-cancer.biomedcentral.com/articles/10.1186/1476-4598-12-86|journal=Molecular Cancer|language=en|volume=12|issue=1|pages=86|doi=10.1186/1476-4598-12-86|issn=1476-4598|pmc=PMC3750319|pmid=23915189}}</ref><ref>{{Cite journal|last=Liu|first=Ting|last2=Zhang|first2=Lingyun|last3=Joo|first3=Donghyun|last4=Sun|first4=Shao-Cong|date=2017-12|title=NF-κB signaling in inflammation|url=http://www.nature.com/articles/sigtrans201723|journal=Signal Transduction and Targeted Therapy|language=en|volume=2|issue=1|pages=17023|doi=10.1038/sigtrans.2017.23|issn=2059-3635|pmc=PMC5661633|pmid=29158945}}</ref> dan respons kerusakan DNA sistemik yang mengarah pada keganasan.<ref>{{Cite journal|last=Ermolaeva|first=Maria A.|last2=Dakhovnik|first2=Alexander|last3=Schumacher|first3=Björn|date=2015-09|title=Quality control mechanisms in cellular and systemic DNA damage responses|url=https://pubmed.ncbi.nlm.nih.gov/25560147|journal=Ageing Research Reviews|volume=23|issue=Pt A|pages=3–11|doi=10.1016/j.arr.2014.12.009|issn=1872-9649|pmc=4886828|pmid=25560147}}</ref>
 
Beberapa penelitian eksperimental dan klinis telah menunjukkan bahwa penyimpangan dan deregulasi UPS berkontribusi pada patogenesis beberapa gangguan neurodegeneratif dan myodegeneratif, termasuk penyakit Alzheimer,<ref>{{Cite journal|last=Checler|first=F.|last2=da Costa|first2=C. A.|last3=Ancolio|first3=K.|last4=Chevallier|first4=N.|last5=Lopez-Perez|first5=E.|last6=Marambaud|first6=P.|date=2000-07-26|title=Role of the proteasome in Alzheimer's disease|url=https://pubmed.ncbi.nlm.nih.gov/10899438|journal=Biochimica Et Biophysica Acta|volume=1502|issue=1|pages=133–138|doi=10.1016/s0925-4439(00)00039-9|issn=0006-3002|pmid=10899438}}</ref> penyakit Parkinson,<ref name = Zhang/>{{Cite journal|last=ChungZheng|first=K. K.Qiuyang|last2=DawsonHuang|first2=V. L.Timothy|last3=DawsonZhang|first3=T. M.Lishan|last4=Zhou|first4=Ying|last5=Luo|first5=Hong|last6=Xu|first6=Huaxi|last7=Wang|first7=Xin|date=20012016-1112-15|title=The roleDysregulation of the ubiquitinUbiquitin-proteasomalProteasome pathwaySystem in Parkinson'sNeurodegenerative disease and other neurodegenerative disordersDiseases|url=httpshttp://pubmedjournal.ncbifrontiersin.nlmorg/article/10.nih3389/fnagi.gov2016.00303/11881748full|journal=TrendsFrontiers in NeurosciencesAging Neuroscience|volume=24|issue=11 Suppl|pages=S7–148|doi=10.10163389/s0166-2236(00)01998-6fnagi.2016.00303|issn=01661663-22364365|pmc=PMC5156861|pmid=1188174828018215}}</ref> dan penyakit Pick,<ref name=Jansen>{{Cite journal|last=IkedaJansen|first=KenjiAnne H. P.|last2=AkiyamaReits|first2=HaruhikoEric A. J.|last3=AraiHol|first3=Tetsuaki|last4=Ueno|first4=Hideki|last5=Tsuchiya|first5=Kuniaki|last6=Kosaka|first6=KenjiElly M.|date=20022014-0708-08|title=MorphometricalThe reappraisalubiquitin of motor neuronproteasome system ofin Pick's diseaseglia and amyotrophicits lateralrole sclerosisin withneurodegenerative dementiadiseases|url=httpshttp://pubmedjournal.ncbifrontiersin.nlmorg/article/10.nih3389/fnmol.gov2014.00073/12070660abstract|journal=ActaFrontiers Neuropathologicain Molecular Neuroscience|volume=104|issue=1|pages=21–287|doi=10.10073389/s00401-001-0513-5fnmol.2014.00073|issn=00011662-63225099|pmc=PMC4126450|pmid=1207066025152710}}</ref> amyotrophic lateral sclerosis (ALS),<ref>{{Cite journal|last=IkedaOpattova|first=KenjiAlena|last2=AkiyamaCente|first2=HaruhikoMartin|last3=AraiNovak|first3=TetsuakiMichal|last4=UenoFilipcik|first4=Hideki|last5=Tsuchiya|first5=Kuniaki|last6=Kosaka|first6=KenjiPeter|date=20022015-0710|title=MorphometricalThe reappraisalubiquitin ofproteasome motorsystem neuronas systema ofpotential Pick'stherapeutic diseasetarget andfor amyotrophictreatment lateralof sclerosis withneurodegenerative dementiadiseases|url=https://pubmed.ncbi.nlm.nih.gov/1207066026221742|journal=ActaGeneral Physiology and NeuropathologicaBiophysics|volume=10434|issue=14|pages=21–28337–352|doi=10.10074149/s00401-001-0513-5gpb_2015024|issn=00010231-63225882|pmid=1207066026221742}}</ref> penyakitamyotrophic lateral sclerosis Huntington(ALS),<ref>{{Cite journal|lastname=Chung|first=K.Jansen/> K.|last2=Dawson|first2=V.penyakit L.|last3=Dawson|first3=T.Huntington,<ref M.|date=2001-11|title=Thename role of the ubiquitin-proteasomal pathway in Parkinson's disease and other neurodegenerative disorders|url=https://pubmed.ncbi.nlm.nih.gov/11881748|journal=Trends in Neurosciences|volume=24|issue=11 Suppl|pages=S7–14|doi=10.1016Zhang/s0166-2236(00)01998-6|issn=0166-2236|pmid=11881748}}</ref> penyakit Creutzfeldt-Jakob,<ref>{{Cite journal|last=ManakaDeriziotis|first=H.Pelagia|last2=KatoTabrizi|first2=T.|last3=Kurita|first3=K.|last4=Katagiri|first4=T.|last5=Shikama|first5=Y.|last6=Kujirai|first6=K.|last7=Kawanami|first7=T.|last8=Suzuki|first8=Y.|last9=Nihei|first9=KSarah J.|date=19922008-05-1112|title=MarkedPrions increaseand inthe cerebrospinal fluid ubiquitin in Creutzfeldt-Jakob diseaseproteasome|url=https://pubmedlinkinghub.ncbielsevier.nlm.nih.govcom/retrieve/pii/1328965S0925443908001336|journal=NeuroscienceBiochimica Letterset Biophysica Acta (BBA) - Molecular Basis of Disease|language=en|volume=1391782|issue=112|pages=47–49713–722|doi=10.1016/0304-3940(92)90854-z|issn=0304-3940|pmid=1328965j.bbadis.2008.06.011}}</ref> dan penyakit neuron motorik, penyakit poliglutamin (PolyQ), distrofi otot,<ref>{{Cite journal|last=MathewsZhu|first=Katherine D.Ting|last2=MooreHayat Khan|first2=Steven A.Sher|last3=Zhao|first3=Deming|last4=Yang|first4=Lifeng|date=20032014-0107|title=Limb-girdleRegulation muscularof dystrophyproteasomes in prion disease|url=https://pubmedacademic.ncbioup.nlmcom/abbs/article-lookup/doi/10.nih.gov1093/12507416abbs/gmu031|journal=CurrentActa NeurologyBiochimica andet NeuroscienceBiophysica ReportsSinica|language=en|volume=346|issue=17|pages=78–85531–539|doi=10.10071093/s11910-003-0042-9abbs/gmu031|issn=15281745-4042|pmid=125074167270}}</ref> dan beberapa bentuk penyakit neurodegeneratif yang jarang terkait dengan demensia.<ref>{{Cite journal|lastname=Mayer|first=R. John|date=2003-03|title=From neurodegeneration to neurohomeostasis: the role of ubiquitin|url=https://pubmed.ncbi.nlm.nih.gov/12792671|journal=Drug News & Perspectives|volume=16|issue=2|pages=103–108|doi=10.1358/dnp.2003.16.2.829327|issn=0214-0934|pmid=12792671}}</refJansen>
 
Sebagai bagian dari sistem ubiquitin-proteasom (UPS), proteasom mempertahankan homeostasis protein jantung dan dengan demikian memainkan peran penting dalam cedera iskemik jantung,<ref>{{Cite journal|last=Calise|first=Justine|last2=Powell|first2=Saul R.|date=2013-02-01|title=The ubiquitin proteasome system and myocardial ischemia|url=https://pubmed.ncbi.nlm.nih.gov/23220331|journal=American Journal of Physiology. Heart and Circulatory Physiology|volume=304|issue=3|pages=H337–349|doi=10.1152/ajpheart.00604.2012|issn=1522-1539|pmc=3774499|pmid=23220331}}</ref> hipertrofi ventrikel,<ref>{{Cite journal|last=Predmore|first=Jaime M.|last2=Wang|first2=Ping|last3=Davis|first3=Frank|last4=Bartolone|first4=Sarah|last5=Westfall|first5=Margaret V.|last6=Dyke|first6=David B.|last7=Pagani|first7=Francis|last8=Powell|first8=Saul R.|last9=Day|first9=Sharlene M.|date=2010-03-02|title=Ubiquitin proteasome dysfunction in human hypertrophic and dilated cardiomyopathies|url=https://pubmed.ncbi.nlm.nih.gov/20159828|journal=Circulation|volume=121|issue=8|pages=997–1004|doi=10.1161/CIRCULATIONAHA.109.904557|issn=1524-4539|pmc=2857348|pmid=20159828}}</ref> dan gagal jantung.<ref>{{Cite journal|last=Powell|first=Saul R.|date=2006-07|title=The ubiquitin-proteasome system in cardiac physiology and pathology|url=https://pubmed.ncbi.nlm.nih.gov/16501026|journal=American Journal of Physiology. Heart and Circulatory Physiology|volume=291|issue=1|pages=H1–H19|doi=10.1152/ajpheart.00062.2006|issn=0363-6135|pmid=16501026}}</ref>
 
Selain itu, bukti terakumulasi bahwa UPS memainkan peran penting dalam transformasi keganasan. Proteolisis UPS memainkan peran utama dalam respons sel kanker terhadap sinyal stimulasi yang sangat penting untuk perkembangan kanker. Oleh karena itu, ekspresi gen melalui degradasi faktor transkripsi, seperti p53, c-jun, c-Fos, NF-κB, c-Myc, HIF-1α, MATα2, STAT3, protein pengikat elemen yang diatur sterol dan reseptor androgen semuanya dikendalikan oleh UPS dan dengan demikian terlibat dalam perkembangan berbagai keganasan.<ref>{{Cite journal|last=AdamsAlmond|first=JulianJb|last2=Cohen|first2=Gm|date=20032002-04|title=The proteasome: a novel target for cancer chemotherapy|url=http://www.nature.com/articles/2402417|journal=Leukemia|language=en|volume=16|issue=4|pages=433–443|doi=10.1038/sj.leu.2402417|issn=0887-016924}}</ref><ref>{{Cite journal|last=Bunn|first=Paul A.|date=2004-06-15|title=The Potential forRole proteasomeof Proteasome inhibitionInhibitors in the treatmentTreatment of cancerLung Cancer|url=httpshttp://pubmedclincancerres.ncbiaacrjournals.nlmorg/lookup/doi/10.nih.gov1158/126545431078-0432.CCR-040011|journal=DrugClinical DiscoveryCancer TodayResearch|language=en|volume=810|issue=712|pages=307–3154263s–4265s|doi=10.10161158/s13591078-6446(03)026470432.CCR-3040011|issn=13591078-6446|pmid=126545430432}}</ref> Selain itu, UPS mengatur degradasi produk gen supresor tumor seperti adenomatous polyposis coli (APC) pada kanker kolorektal, retinoblastoma (Rb), dan penekan tumor von Hippel–Lindau (VHL), serta sejumlah proto-onkogen (Raf, Myc, Myb, Rel, Src, Mos, ABL). UPS juga terlibat dalam regulasi respon inflamasi. Aktivitas ini biasanya dikaitkan dengan peran proteasom dalam aktivasi NF-κB yang selanjutnya mengatur ekspresi sitokin pro-inflamasi seperti TNF-α, IL-β, IL-8, molekul adhesi (ICAM-1, VCAM-1, P-selektin), prostaglandin, dan oksida nitrat (NO).<ref name = Hoesel/> Selain itu, UPS juga berperan dalam respons inflamasi sebagai pengatur proliferasi leukosit, terutama melalui proteolisis siklin dan degradasi inhibitor CDK.<ref>{{Cite journal|last=Ben-NeriahZhu|first=YinonBo|last2=Zhu|first2=Lihua|last3=Xia|first3=Lin|last4=Xiong|first4=Yuyun|last5=Yin|first5=Qing|last6=Rui|first6=Ke|date=20022020-0111-16|title=Regulatory functionsRoles of ubiquitinationUbiquitination and Deubiquitination in theRegulating Dendritic Cell Maturation immuneand systemFunction|url=https://pubmedwww.ncbifrontiersin.nlmorg/articles/10.3389/fimmu.nih2020.gov586613/11753406full|journal=NatureFrontiers in Immunology|volume=3|issue=111|pages=20–26586613|doi=10.10383389/ni0102-20fimmu.2020.586613|issn=15291664-29083224|pmidpmc=11753406PMC7717991|}}</ref> Terakhir, pasien penyakit autoimun dengan SLE, sindrom Sjögren dan rheumatoid arthritis (RA) secara dominan menunjukkan proteasom yang bersirkulasi yang dapat diterapkan sebagai biomarker klinis.<ref>{{Cite journal|last=Egerer|first=Karl|last2=Kuckelkorn|first2=Ulrike|last3=Rudolph|first3=Paul E.|last4=Rückert|first4=Jens C.|last5=Dörner|first5=Thomas|last6=Burmester|first6=Gerd-R.|last7=Kloetzel|first7=Peter-M.|last8=Feist|first8=Eugen|date=2002-10|title=Circulating proteasomes are markers of cell damage and immunologic activity in autoimmune diseases|url=https://pubmed.ncbi.nlm.nih.gov/12375310|journal=The Journal of Rheumatology|volume=29|issue=10|pages=2045–2052|issn=0315-162X|pmid=12375310}}</ref>
 
==Inhibitor proteasom ==
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Inhibitor proteasom memiliki aktivitas anti-tumor yang efektif dalam kultur sel yaitu menginduksi [[apoptosis]] dengan mengganggu degradasi yang diatur dari protein siklus sel pro-pertumbuhan. Pendekatan selektif menginduksi apoptosis dalam sel tumor telah terbukti efektif dalam model hewan dan percobaan manusia.
 
'''Laktasistin''', suatu produk alami yang disintesis oleh bakteri ''Streptomyces'', merupakan inhibitor proteasom non-peptida pertama yang ditemukan,<ref>{{Cite journal|last=FenteanyŌmura|first=G.Satoshi|last2=StandaertCrump|first2=R. F.|last3=Lane|first3=W. S.|last4=Choi|first4=S.|last5=Corey|first5=E. J.|last6=Schreiber|first6=S. L.Andy|date=19952019-05-0504|title=InhibitionLactacystin: offirst-in-class proteasome activitiesinhibitor still excelling and subunit-specifican amino-terminalexemplar threoninefor modificationfuture byantibiotic lactacystinresearch|url=httpshttp://pubmedwww.ncbinature.nlm.nih.govcom/7732382articles/s41429-019-0141-8|journal=ScienceThe (NewJournal York,of N.Y.)Antibiotics|language=en|volume=26872|issue=52114|pages=726–731189–201|doi=10.11261038/science.7732382s41429-019-0141-8|issn=00360021-80758820|pmc=PMC6760633|pmid=773238230755736}}</ref> dan digunakan secara luas sebagai bahan penelitian dalam biokimia dan biologi sel. Laktasistin secara kovalen memodifikasi treonin terminal amino dari subunit katalitik dari proteasom, khususnya subunit 5 yang bertanggung jawab atas aktivitas mirip kimotripsin proteasom. Penemuan ini membantu menetapkan proteasom sebagai kelas protease baru yang mekanistik: protease treonin terminal amino.
 
'''Bortezomib '''(Boronated MG132), sebuah molekul yang dipasarkan sebagai Velcade, adalah inhibitor proteasom pertama yang dalam penggunaan klinis sebagai agen kemoterapi. Bortezomib digunakan dalam pengobatan multiple myeloma.<ref>{{Cite journal|last=Fisher|first=Richard I.|last2=Bernstein|first2=Steven H.|last3=Kahl|first3=Brad S.|last4=Djulbegovic|first4=Benjamin|last5=Robertson|first5=Michael J.|last6=de Vos|first6=Sven|last7=Epner|first7=Elliot|last8=Krishnan|first8=Amrita|last9=Leonard|first9=John P.|date=2006-10-20|title=Multicenter phase II study of bortezomib in patients with relapsed or refractory mantle cell lymphoma|url=https://pubmed.ncbi.nlm.nih.gov/17001068|journal=Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology|volume=24|issue=30|pages=4867–4874|doi=10.1200/JCO.2006.07.9665|issn=1527-7755|pmid=17001068}}</ref> Khususnya, multiple myeloma telah diamati menghasilkan peningkatan kadar peptida turunan proteasom dalam serum darah yang menurun ke tingkat normal sebagai respons terhadap kemoterapi yang berhasil.<ref>{{Cite journal|last=Jakob|first=Christian|last2=Egerer|first2=Karl|last3=Liebisch|first3=Peter|last4=Türkmen|first4=Seval|last5=Zavrski|first5=Ivana|last6=Kuckelkorn|first6=Ulrike|last7=Heider|first7=Ulrike|last8=Kaiser|first8=Martin|last9=Fleissner|first9=Claudia|date=2007-03-01|title=Circulating proteasome levels are an independent prognostic factor for survival in multiple myeloma|url=https://pubmed.ncbi.nlm.nih.gov/17095627|journal=Blood|volume=109|issue=5|pages=2100–2105|doi=10.1182/blood-2006-04-016360|issn=0006-4971|pmid=17095627}}</ref> Penelitian pada hewan telah menunjukkan bahwa bortezomib dapat juga memiliki efek klinis yang signifikan pada kanker pankreas.<ref>{{Cite journal|last=Shah|first=S. A.|last2=Potter|first2=M. W.|last3=McDade|first3=T. P.|last4=Ricciardi|first4=R.|last5=Perugini|first5=R. A.|last6=Elliott|first6=P. J.|last7=Adams|first7=J.|last8=Callery|first8=M. P.|date=2001 Apr 2-27|title=26S proteasome inhibition induces apoptosis and limits growth of human pancreatic cancer|url=https://pubmedwww.ncbiacademia.nlm.nih.govedu/1140016825612539/26S_proteasome_inhibition_induces_apoptosis_and_limits_growth_of_human_pancreatic_cancer|journal=Journal of Cellular Biochemistry|volume=82|issue=1|pages=110–122|doi=10.1002/jcb.1150|issn=0730-2312|pmid=11400168}}</ref><ref>{{Cite journal|last=Nawrocki|first=Steffan T.|last2=Sweeney-Gotsch|first2=Bridget|last3=Takamori|first3=Ryan|last4=McConkey|first4=David J.|date=2004-01|title=The proteasome inhibitor bortezomib enhances the activity of docetaxel in orthotopic human pancreatic tumor xenografts|url=https://pubmed.ncbi.nlm.nih.gov/14749476|journal=Molecular Cancer Therapeutics|volume=3|issue=1|pages=59–70|issn=1535-7163|pmid=14749476}}</ref> Penelitian pra-klinis dan klinis awal telah dimulai untuk menguji efektivitas bortezomib dalam mengobati kanker terkait sel B lainnya,<ref>{{Cite journal|last=SchenkeinLiu|first=DavidWei|last2=Chen|first2=Juan|last3=Tamayo|first3=Archito T.|last4=Ruan|first4=Changgeng|last5=Li|first5=Li|last6=Zhou|first6=Shouhao|last7=Shen|first7=Chan|last8=Young|first8=Ken H.|last9=Westin|first9=Jason|date=20022018-0601-02|title=ProteasomePreclinical inhibitorsefficacy inand thebiological treatmenteffects of the oral proteasome inhibitor ixazomib in diffuse large B-cell malignancieslymphoma|url=https://pubmedwww.ncbioncotarget.nlmcom/lookup/doi/10.nih18632/oncotarget.gov/1214195620378|journal=Clinical LymphomaOncotarget|language=en|volume=39|issue=1|pages=49–55346–360|doi=10.381618632/clmoncotarget.2002.n.01120378|issn=15261949-96552553|pmc=PMC5787470|pmid=1214195629416618}}</ref> khususnya beberapa jenis limfoma non-Hodgkin.<ref>{{Cite journal|last=O'Connor|first=Owen A.|last2=Wright|first2=John|last3=Moskowitz|first3=Craig|last4=Muzzy|first4=Jamie|last5=MacGregor-Cortelli|first5=Barbara|last6=Stubblefield|first6=Michael|last7=Straus|first7=David|last8=Portlock|first8=Carol|last9=Hamlin|first9=Paul|date=2005-02-01|title=Phase II clinical experience with the novel proteasome inhibitor bortezomib in patients with indolent non-Hodgkin's lymphoma and mantle cell lymphoma|url=https://pubmed.ncbi.nlm.nih.gov/15613699|journal=Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology|volume=23|issue=4|pages=676–684|doi=10.1200/JCO.2005.02.050|issn=0732-183X|pmid=15613699}}</ref> Hasil klinis juga tampaknya membenarkan penggunaan inhibitor proteasom yang dikombinasikan dengan kemoterapi, untuk leukemia limfoblastik akut sel B.<ref>{{Cite journal|last=Messinger|first=Yoav H.|last2=Gaynon|first2=Paul S.|last3=Sposto|first3=Richard|last4=van der Giessen|first4=Jeannette|last5=Eckroth|first5=Elena|last6=Malvar|first6=Jemily|last7=Bostrom|first7=Bruce C.|last8=Therapeutic Advances in Childhood Leukemia & Lymphoma (TACL) Consortium|date=2012-07-12|title=Bortezomib with chemotherapy is highly active in advanced B-precursor acute lymphoblastic leukemia: Therapeutic Advances in Childhood Leukemia & Lymphoma (TACL) Study|url=https://pubmed.ncbi.nlm.nih.gov/22653976|journal=Blood|volume=120|issue=2|pages=285–290|doi=10.1182/blood-2012-04-418640|issn=1528-0020|pmid=22653976}}</ref> Inhibitor proteasom dapat membunuh beberapa jenis sel leukemia yang resisten terhadap glukokortikoid.<ref>{{Cite journal|last=LambrouPufall|first=George I.|last2=Papadimitriou|first2=Lina|last3=Chrousos|first3=George P.|last4=Vlahopoulos|first4=SpirosMiles A.|date=2012-042015|title=GlucocorticoidGlucocorticoids and proteasome inhibitor impact on the leukemic lymphoblast: Multiple, diverse signals converging on a few key downstream regulatorsCancer|url=https://linkinghubpubmed.elsevierncbi.nlm.comnih.gov/retrieve/pii/S030372071200007X26216001|journal=MolecularAdvances in Experimental Medicine and Cellular Endocrinology|language=enBiology|volume=351|issue=2872|pages=142–151315–333|doi=10.10161007/j.mce.2012.01.003978-1-4939-2895-8_14|issn=0065-2598|pmc=5546099|pmid=26216001}}</ref>
 
Ritonavir dikembangkan sebagai [[inhibitor protease]] dan digunakan untuk menargetkan infeksi HIV. Namun, telah terbukti menghambat proteasom serta protease bebas; secara spesifik, aktivitas proteasom yang mirip kimotripsin dihambat oleh ritonavir, sedangkan aktivitas mirip tripsin agak meningkat.<ref>{{Cite journal|last=Schmidtke|first=G.|last2=Holzhütter|first2=H. G.|last3=Bogyo|first3=M.|last4=Kairies|first4=N.|last5=Groll|first5=M.|last6=de Giuli|first6=R.|last7=Emch|first7=S.|last8=Groettrup|first8=M.|date=1999-12-10|title=How an inhibitor of the HIV-I protease modulates proteasome activity|url=https://pubmed.ncbi.nlm.nih.gov/10585454|journal=The Journal of Biological Chemistry|volume=274|issue=50|pages=35734–35740|doi=10.1074/jbc.274.50.35734|issn=0021-9258|pmid=10585454}}</ref> Studi pada model hewan menunjukkan bahwa ritonavir mungkin memiliki efek penghambatan pada pertumbuhan sel glioma.<ref>{{Cite journal|last=Laurent|first=Nathalie|last2=de Boüard|first2=Sophie|last3=Guillamo|first3=Jean-Sébastien|last4=Christov|first4=Christo|last5=Zini|first5=Roland|last6=Jouault|first6=Hélène|last7=Andre|first7=Patrice|last8=Lotteau|first8=Vincent|last9=Peschanski|first9=Marc|date=2004-02|title=Effects of the proteasome inhibitor ritonavir on glioma growth in vitro and in vivo|url=https://pubmedaacrjournals.ncbi.nlm.nih.govorg/mct/article/3/2/129/234309/14985453Effects-of-the-proteasome-inhibitor-ritonavir-on|journal=Molecular Cancer Therapeutics|volume=3|issue=2|pages=129–136|issn=1535-7163|pmid=14985453}}</ref>
 
Inhibitor proteasom juga menjanjikan dalam mengobati [[penyakit autoimun]] pada model hewan. Misalnya, penelitian pada tikus yang membawa cangkok kulit manusia menemukan pengurangan ukuran lesi dari [[psoriasis]] setelah pengobatan dengan inhibitor proteasom.<ref>{{Cite journal|last=Zollner|first=Thomas M.|last2=Podda|first2=Maurizio|last3=Pien|first3=Christine|last4=Elliott|first4=Peter J.|last5=Kaufmann|first5=Roland|last6=Boehncke|first6=Wolf-Henning|date=2002-03|title=Proteasome inhibition reduces superantigen-mediated T cell activation and the severity of psoriasis in a SCID-hu model|url=https://pubmed.ncbi.nlm.nih.gov/11877475|journal=The Journal of Clinical Investigation|volume=109|issue=5|pages=671–679|doi=10.1172/JCI12736|issn=0021-9738|pmc=PMC150886|pmid=11877475}}</ref> Inhibitor juga menunjukkan efek positif pada model [[asma]] tikus.<ref>{{Cite journal|last=Elliott|first=P. J.|last2=Pien|first2=C. S.|last3=McCormack|first3=T. A.|last4=Chapman|first4=I. D.|last5=Adams|first5=J.|date=1999-08|title=Proteasome inhibition: A novel mechanism to combat asthma|url=https://pubmed.ncbi.nlm.nih.gov/10452747|journal=The Journal of Allergy and Clinical Immunology|volume=104|issue=2 Pt 1|pages=294–300|doi=10.1016/s0091-6749(99)70369-6|issn=0091-6749|pmid=10452747}}</ref> Bahan-bahan dari alam saat ini juga dilirik karena potensi aksinya sebagai inhibitor proteasom.<ref>{{Cite journal|last=Hubbell|first=Grace E.|last2=Tepe|first2=Jetze J.|date=2020|title=Natural product scaffolds as inspiration for the design and synthesis of 20S human proteasome inhibitors|url=http://xlink.rsc.org/?DOI=D0CB00111B|journal=RSC Chemical Biology|language=en|volume=1|issue=5|pages=305–332|doi=10.1039/D0CB00111B|issn=2633-0679|}}</ref>
 
Pelabelan dan inhibitor proteasom juga menarik dalam laboratorium untuk studi aktivitas proteasomal dalam sel in vitro dan in vivo. Inhibitor proteasom yang paling umum digunakan yaitu laktasistin dan peptida aldehid MG132 yang awalnya dikembangkan oleh laboratorium Goldberg. Inhibitor fluoresen juga telah dikembangkan untuk secara khusus memberi label pada situs aktif dari proteasom yang dirakit.[116]
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