RAD23B
Homolog B UV-ekscizijskog popravka proteina RAD23 jest protein koji je kod ljudi kodiran genom RAD23B sa hromosoma 9.[5][6]
Aminokiselinska sekvenca
[uredi | uredi izvor]Dužina polipeptidnog lanca je 409 aminokiselina, a molekulska težina 43.171 Da.[6]
| 10 | 20 | 30 | 40 | 50 | ||||
|---|---|---|---|---|---|---|---|---|
| MQVTLKTLQQ | QTFKIDIDPE | ETVKALKEKI | ESEKGKDAFP | VAGQKLIYAG | ||||
| KILNDDTALK | EYKIDEKNFV | VVMVTKPKAV | STPAPATTQQ | SAPASTTAVT | ||||
| SSTTTTVAQA | PTPVPALAPT | STPASITPAS | ATASSEPAPA | SAAKQEKPAE | ||||
| KPAETPVATS | PTATDSTSGD | SSRSNLFEDA | TSALVTGQSY | ENMVTEIMSM | ||||
| GYEREQVIAA | LRASFNNPDR | AVEYLLMGIP | GDRESQAVVD | PPQAASTGAP | ||||
| QSSAVAAAAA | TTTATTTTTS | SGGHPLEFLR | NQPQFQQMRQ | IIQQNPSLLP | ||||
| ALLQQIGREN | PQLLQQISQH | QEHFIQMLNE | PVQEAGGQGG | GGGGGSGGIA | ||||
| EAGSGHMNYI | QVTPQEKEAI | ERLKALGFPE | GLVIQAYFAC | EKNENLAANF | ||||
| LLQQNFDED |
Funkcija
[uredi | uredi izvor]Protein kodiran ovim genom jedan je od dva ljudska homologa Saccharomyces cerevisiae Rad23, proteina uključenog u popravak ekscizijom nukleotida (NER). Utvrđeno je da je ovaj protein komponenta proteinskog kompleksa koji specifično nadopunjuje NER defekt ekstrakta ćelija xeroderma pigmentosum grupe C (XP-c) in vitro. Pokazalo se i da ovaj protein stupa u interakciju sa i podiže ekscizijsku aktivnost 3-metiladenin-DNK glikozilaznog (MPG) nukleotida, što ukazuje na ulogu u prepoznavanju oštećenja DNK u popravci ekscizijom baze. Ovaj protein sadrži N-terminalni domen sličan ubikvitinu, za koji je objavljeno da interragira sa proteasomom 26S, te stoga ovaj protein može biti uključen u proteolitski put u ćelijama, posredovan ubikvitinom.[7]
Uloga u popravku DNK
[uredi | uredi izvor]Kompleks XPC-RAD23B je početni faktor prepoznavanja oštećenja u globalnom popravku ekscizijom genomskih nukleotida (GG-NER). XPC-RAD23B prepoznaje širok spektar lezija koje termodinamički destabiliziraju DNK duplekse, uključujući UV-inducirane fotoproizvode (ciklopirimidinski dimeri i 6-4 fotoproizvodi), adukte formirane mutagenima iz okoliša, kao što su benzo[a]piren ili različiti aromatski amini, određene oksidativnne endogene lezije kao što su ciklopurini i adukti formirani hemoterapijskim lijekovima protiv raka kao što je cisplatin. Prisustvo XPC-RAD23B je potrebno za sklapanje drugih jedarnih faktora NER i progresiju kroz NER put i in vitro i in vivo.[8] Although most studies have been performed with XPC-RAD23B, it is part of a trimeric complex with centrin-2, a calcium-binding protein of the calmodulin family.[8]
Epigenetička represija
[uredi | uredi izvor]Nivo ekspresije proteina RAD23B može biti epigenetički potisnut, bilo promotora metilacije gena RAD23B [9][10] ili bilo kojom od dvije mikroRNK (miR -744-3p[11] ili miR-373.[12])
Nedostatak RAD23B kod raka
[uredi | uredi izvor]Nedostatak ekspresije gena za popravak DNK povećava rizik od raka (pogledajte nedostatak popravka DNK u karcinogenezi). Ekspresija RAD23B je smanjena u tumorskom tkivu žena sa rakom dojke.[13] Uočen je i nizak postotak RAD23B pozitivnih jedara kod raka dojke visokog stepena.[14]
RAD23B je značajno smanjen metilacijama promotora u ćelijskoj liniji koja potiče od multiplog mijeloma.[9] i smanjen metilacijom promotora u malom udjelu [[rak pluća nemalih ćelija|raka pluća nemalih ćelijaa (NSCLC) tumours.[10]
Čini se da je RAD23B jedan od 26 gena za popravak DNK koji su epigenetički potisnuti kod različitih karcinoma (vidi Epigenetika raka).
Interakcije
[uredi | uredi izvor]Pokazano je da RAD23B u interakcijama sa PSMD4[15] i ataksinom 3.[16]
Reference
[uredi | uredi izvor]- ^ a b c GRCh38: Ensembl release 89: ENSG00000119318 - Ensembl, maj 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000028426 - Ensembl, maj 2017
- ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ van der Spek PJ, Smit EM, Beverloo HB, Sugasawa K, Masutani C, Hanaoka F, Hoeijmakers JH, Hagemeijer A (Oct 1994). "Chromosomal localization of three repair genes: the xeroderma pigmentosum group C gene and two human homologs of yeast RAD23". Genomics. 23 (3): 651–8. doi:10.1006/geno.1994.1554. hdl:1765/3069. PMID 7851894.
- ^ a b Masutani C, Sugasawa K, Yanagisawa J, Sonoyama T, Ui M, Enomoto T, Takio K, Tanaka K, van der Spek PJ, Bootsma D (Apr 1994). "Purification and cloning of a nucleotide excision repair complex involving the xeroderma pigmentosum group C protein and a human homologue of yeast RAD23". The EMBO Journal. 13 (8): 1831–43. doi:10.1002/j.1460-2075.1994.tb06452.x. PMC 395023. PMID 8168482.
- ^ "Entrez Gene: RAD23B RAD23 homolog B (S. cerevisiae)".
- ^ a b Schärer OD (Oct 2013). "Nucleotide excision repair in eukaryotes". Cold Spring Harbor Perspectives in Biology. 5 (10): a012609. doi:10.1101/cshperspect.a012609. PMC 3783044. PMID 24086042.
- ^ a b Peng B, Hodge DR, Thomas SB, Cherry JM, Munroe DJ, Pompeia C, Xiao W, Farrar WL (Feb 2005). "Epigenetic silencing of the human nucleotide excision repair gene, hHR23B, in interleukin-6-responsive multiple myeloma KAS-6/1 cells". The Journal of Biological Chemistry. 280 (6): 4182–7. doi:10.1074/jbc.M412566200. PMID 15550378.
- ^ a b Do H, Wong NC, Murone C, John T, Solomon B, Mitchell PL, Dobrovic A (2014). "A critical re-assessment of DNA repair gene promoter methylation in non-small cell lung carcinoma". Scientific Reports. 4: 4186. Bibcode:2014NatSR...4E4186D. doi:10.1038/srep04186. PMC 3935198. PMID 24569633.
- ^ Hatano K, Kumar B, Zhang Y, Coulter JB, Hedayati M, Mears B, Ni X, Kudrolli TA, Chowdhury WH, Rodriguez R, DeWeese TL, Lupold SE (Apr 2015). "A functional screen identifies miRNAs that inhibit DNA repair and sensitize prostate cancer cells to ionizing radiation". Nucleic Acids Research. 43 (8): 4075–86. doi:10.1093/nar/gkv273. PMC 4417178. PMID 25845598.
- ^ Crosby ME, Kulshreshtha R, Ivan M, Glazer PM (Feb 2009). "MicroRNA regulation of DNA repair gene expression in hypoxic stress". Cancer Research. 69 (3): 1221–9. doi:10.1158/0008-5472.CAN-08-2516. PMC 2997438. PMID 19141645.
- ^ Matta J, Morales L, Dutil J, Bayona M, Alvarez C, Suarez E (Feb 2013). "Differential expression of DNA repair genes in Hispanic women with breast cancer". Molecular Cancer Biology. 1 (1): 54. doi:10.9777/mcb.2013.10006 (neaktivno 31. 12. 2022). PMC 4189824. PMID 25309843.CS1 održavanje: DOI nije aktivan od 2022 (link)
- ^ Linge A, Maurya P, Friedrich K, Baretton GB, Kelly S, Henry M, Clynes M, Larkin A, Meleady P (Jul 2014). "Identification and functional validation of RAD23B as a potential protein in human breast cancer progression". Journal of Proteome Research. 13 (7): 3212–22. doi:10.1021/pr4012156. PMID 24897598.
- ^ Hiyama H, Yokoi M, Masutani C, Sugasawa K, Maekawa T, Tanaka K, Hoeijmakers JH, Hanaoka F (Sep 1999). "Interaction of hHR23 with S5a. The ubiquitin-like domain of hHR23 mediates interaction with S5a subunit of 26 S proteasome" (PDF). The Journal of Biological Chemistry. 274 (39): 28019–25. doi:10.1074/jbc.274.39.28019. PMID 10488153. S2CID 1757366.
- ^ Wang G, Sawai N, Kotliarova S, Kanazawa I, Nukina N (Jul 2000). "Ataxin-3, the MJD1 gene product, interacts with the two human homologs of yeast DNA repair protein RAD23, HHR23A and HHR23B". Human Molecular Genetics. 9 (12): 1795–803. doi:10.1093/hmg/9.12.1795. PMID 10915768.
Dopunska literatura
[uredi | uredi izvor]- Maruyama K, Sugano S (Jan 1994). "Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides". Gene. 138 (1–2): 171–4. doi:10.1016/0378-1119(94)90802-8. PMID 8125298.
- van der Spek PJ, Eker A, Rademakers S, Visser C, Sugasawa K, Masutani C, Hanaoka F, Bootsma D, Hoeijmakers JH (Jul 1996). "XPC and human homologs of RAD23: intracellular localization and relationship to other nucleotide excision repair complexes". Nucleic Acids Research. 24 (13): 2551–9. doi:10.1093/nar/24.13.2551. PMC 145966. PMID 8692695.
- Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, Suyama A, Sugano S (Oct 1997). "Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library". Gene. 200 (1–2): 149–56. doi:10.1016/S0378-1119(97)00411-3. PMID 9373149.
- Sugasawa K, Ng JM, Masutani C, Iwai S, van der Spek PJ, Eker AP, Hanaoka F, Bootsma D, Hoeijmakers JH (Aug 1998). "Xeroderma pigmentosum group C protein complex is the initiator of global genome nucleotide excision repair". Molecular Cell. 2 (2): 223–32. doi:10.1016/S1097-2765(00)80132-X. PMID 9734359.
- Hiyama H, Yokoi M, Masutani C, Sugasawa K, Maekawa T, Tanaka K, Hoeijmakers JH, Hanaoka F (Sep 1999). "Interaction of hHR23 with S5a. The ubiquitin-like domain of hHR23 mediates interaction with S5a subunit of 26 S proteasome" (PDF). The Journal of Biological Chemistry. 274 (39): 28019–25. doi:10.1074/jbc.274.39.28019. PMID 10488153. S2CID 1757366.
- Miao F, Bouziane M, Dammann R, Masutani C, Hanaoka F, Pfeifer G, O'Connor TR (Sep 2000). "3-Methyladenine-DNA glycosylase (MPG protein) interacts with human RAD23 proteins". The Journal of Biological Chemistry. 275 (37): 28433–8. doi:10.1074/jbc.M001064200. PMID 10854423.
- Wang G, Sawai N, Kotliarova S, Kanazawa I, Nukina N (Jul 2000). "Ataxin-3, the MJD1 gene product, interacts with the two human homologs of yeast DNA repair protein RAD23, HHR23A and HHR23B". Human Molecular Genetics. 9 (12): 1795–803. doi:10.1093/hmg/9.12.1795. PMID 10915768.
- Araújo SJ, Nigg EA, Wood RD (Apr 2001). "Strong functional interactions of TFIIH with XPC and XPG in human DNA nucleotide excision repair, without a preassembled repairosome". Molecular and Cellular Biology. 21 (7): 2281–91. doi:10.1128/MCB.21.7.2281-2291.2001. PMC 86862. PMID 11259578.
- Araki M, Masutani C, Takemura M, Uchida A, Sugasawa K, Kondoh J, Ohkuma Y, Hanaoka F (Jun 2001). "Centrosome protein centrin 2/caltractin 1 is part of the xeroderma pigmentosum group C complex that initiates global genome nucleotide excision repair". The Journal of Biological Chemistry. 276 (22): 18665–72. doi:10.1074/jbc.M100855200. PMID 11279143.
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- Walters KJ, Kleijnen MF, Goh AM, Wagner G, Howley PM (Feb 2002). "Structural studies of the interaction between ubiquitin family proteins and proteasome subunit S5a". Biochemistry. 41 (6): 1767–77. doi:10.1021/bi011892y. PMID 11827521.
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- Shimizu Y, Iwai S, Hanaoka F, Sugasawa K (Jan 2003). "Xeroderma pigmentosum group C protein interacts physically and functionally with thymine DNA glycosylase". The EMBO Journal. 22 (1): 164–73. doi:10.1093/emboj/cdg016. PMC 140069. PMID 12505994.
- Ng JM, Vermeulen W, van der Horst GT, Bergink S, Sugasawa K, Vrieling H, Hoeijmakers JH (Jul 2003). "A novel regulation mechanism of DNA repair by damage-induced and RAD23-dependent stabilization of xeroderma pigmentosum group C protein". Genes & Development. 17 (13): 1630–45. doi:10.1101/gad.260003. PMC 196135. PMID 12815074.
- Ryu KS, Lee KJ, Bae SH, Kim BK, Kim KA, Choi BS (Sep 2003). "Binding surface mapping of intra- and interdomain interactions among hHR23B, ubiquitin, and polyubiquitin binding site 2 of S5a". The Journal of Biological Chemistry. 278 (38): 36621–7. doi:10.1074/jbc.M304628200. PMID 12832454.
- Fujiwara K, Tenno T, Sugasawa K, Jee JG, Ohki I, Kojima C, Tochio H, Hiroaki H, Hanaoka F, Shirakawa M (Feb 2004). "Structure of the ubiquitin-interacting motif of S5a bound to the ubiquitin-like domain of HR23B". The Journal of Biological Chemistry. 279 (6): 4760–7. doi:10.1074/jbc.M309448200. PMID 14585839.
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