NFKBIZ
(Preusmjereno sa NF-kapa-B inhibitor zeta)
NF-kapa-B inhibitor zeta (IκBζ) jest protein koji je kod ljudi kodiran genom NFKBIZ sa hromosoma 3.[5][6][7]
Aminokiselinska sekvenca
urediDužina polipeptidnog lanca je 718 aminokiselina, а molekulska težina 78.061 Da.[8]
| 10 | 20 | 30 | 40 | 50 | ||||
|---|---|---|---|---|---|---|---|---|
| MIVDKLLDDS | RGGEGLRDAA | GGCGLMTSPL | NLSYFYGASP | PAAAPGACDA | ||||
| SCSVLGPSAP | GSPGSDSSDF | SSASSVSSCG | AVESRSRGGA | RAERQPVEPH | ||||
| MGVGRQQRGP | FQGVRVKNSV | KELLLHIRSH | KQKASGQAVD | DFKTQGVNIE | ||||
| QFRELKNTVS | YSGKRKGPDS | LSDGPACKRP | ALLHSQFLTP | PQTPTPGESM | ||||
| EDVHLNEPKQ | ESSADLLQNI | INIKNECSPV | SLNTVQVSWL | NPVVVPQSSP | ||||
| AEQCQDFHGG | QVFSPPQKCQ | PFQVRGSQQM | IDQASLYQYS | PQNQHVEQQP | ||||
| HYTHKPTLEY | SPFPIPPQSP | AYEPNLFDGP | ESQFCPNQSL | VSLLGDQRES | ||||
| ENIANPMQTS | SSVQQQNDAH | LHSFSMMPSS | ACEAMVGHEM | ASDSSNTSLP | ||||
| FSNMGNPMNT | TQLGKSLFQW | QVEQEESKLA | NISQDQFLSK | DADGDTFLHI | ||||
| AVAQGRRALS | YVLARKMNAL | HMLDIKEHNG | QSAFQVAVAA | NQHLIVQDLV | ||||
| NIGAQVNTTD | CWGRTPLHVC | AEKGHSQVLQ | AIQKGAVGSN | QFVDLEATNY | ||||
| DGLTPLHCAV | IAHNAVVHEL | QRNQQPHSPE | VQELLLKNKS | LVDTIKCLIQ | ||||
| MGAAVEAKDR | KSGRTALHLA | AEEANLELIR | LFLELPSCLS | FVNAKAYNGN | ||||
| TALHVAASLQ | YRLTQLDAVR | LLMRKGADPS | TRNLENEQPV | HLVPDGPVGE | ||||
| QIRRILKGKS | IQQRAPPY |
Funkcija
urediOvaj gen je član porodice ankirinskihponavcljanja i induciran je lipopolisaharidom (LPS). C-terminalni dio kodiranog proizvoda koji sadrži ankirinska ponavljanja, dijeli veliku sličnost sa porodicom proteina sa slučnošću sekvence I kapa B. Poznato je da potonji imaju ulogu u upalnim odgovorima na LPS njihovom interakcijom sa NF-B proteinima preko domena za ponavljanje ankirina. Studije na miševima pokazuju da je ovaj genski proizvod jedan od jedarnih I kapa B proteina i aktivator proizvodnje IL-6. Za ovaj gen su pronađene dvije varijante transkripta koje kodiraju različite izoforme.[9]
Klinički značaj
urediNFKBIZ je impliciran kao onkogen u difuznom velikom B-ćelijskom limfomu (DLBCL). Konkretno, genomski lokus koji sadrži ovaj gen se rekurentno umnožava u broju kopija u aktiviranoj B-ćelijskoj (ABC) podgrupi DLBCL.[10] Nedavno je otkriveno da ponavljanje somatskih mutacija koje utjiču na 3-prim neprevedenu regiju NFKBIZ promovira ekspresiju NFKBIZ u ABC DLBCL.[11]
IκBζ potreban je za ekspresiju sekretornog fenotipa povezanog sa starenjem (SASP) CCL2 (MCP1) citokina, koji regrutuje makrofage za uklanjanje ćelija raka.[7]
Pokazalo se da flavonoid apigenin smanjuje ekspresiju gena IκBζ.[12]
Reference
uredi- ^ a b c GRCh38: Ensembl release 89: ENSG00000144802 - Ensembl, maj 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000035356 - 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.
- ^ Eto A, Muta T, Yamazaki S, Takeshige K (februar 2003). "Essential roles for NF-kappa B and a Toll/IL-1 receptor domain-specific signal(s) in the induction of I kappa B-zeta". Biochemical and Biophysical Research Communications. 301 (2): 495–501. doi:10.1016/S0006-291X(02)03082-6. PMID 12565889.
- ^ Totzke G, Essmann F, Pohlmann S, Lindenblatt C, Jänicke RU, Schulze-Osthoff K (maj 2006). "A novel member of the IkappaB family, human IkappaB-zeta, inhibits transactivation of p65 and its DNA binding". The Journal of Biological Chemistry. 281 (18): 12645–54. doi:10.1074/jbc.M511956200. PMID 16513645.
- ^ a b Alexander E, Hildebrand DG, Schulze-Osthoff K, Essmann F (2013). "IκBζ is a regulator of the senescence-associated secretory phenotype in DNA damage- and oncogene-induced senescence". Journal of Cell Science. 126 (Pt 16): 3738–3745. doi:10.1242/jcs.128835. PMID 23781024.
- ^ "UniProt, Q9BYH8" (jezik: engleski). Pristupljeno 8. 11. 2021.
- ^ "Entrez Gene: NFKBIZ nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, zeta".
- ^ Nogai H, Wenzel SS, Hailfinger S, Grau M, Kaergel E, Seitz V, et al. (septembar 2013). "IκB-ζ controls the constitutive NF-κB target gene network and survival of ABC DLBCL". Blood. 122 (13): 2242–50. doi:10.1182/blood-2013-06-508028. PMID 23869088.
- ^ Arthur SE, Jiang A, Grande BM, Alcaide M, Cojocaru R, Rushton CK, et al. (oktobar 2018). "Genome-wide discovery of somatic regulatory variants in diffuse large B-cell lymphoma". Nature Communications. 9 (1): 4001. Bibcode:2018NatCo...9.4001A. doi:10.1038/s41467-018-06354-3. PMC 6167379. PMID 30275490.
- ^ Lim H, Heo MY, Kim HP (2019). "Flavonoids: Broad Spectrum Agents on Chronic Inflammation". Biomolecules & Therapeutics. 27 (3): 241–253. doi:10.4062/biomolther.2019.034. PMC 6513185. PMID 31006180.
Dopunska literatura
uredi- Kitamura H, Kanehira K, Okita K, Morimatsu M, Saito M (novembar 2000). "MAIL, a novel nuclear I kappa B protein that potentiates LPS-induced IL-6 production". FEBS Letters. 485 (1): 53–6. doi:10.1016/S0014-5793(00)02185-2. PMID 11086164. S2CID 85416608.
- Shiina T, Morimatsu M, Kitamura H, Ito T, Kidou S, Matsubara K, Matsuda Y, Saito M, Syuto B (oktobar 2001). "Genomic organization, chromosomal localization, and promoter analysis of the mouse Mail gene". Immunogenetics. 53 (8): 649–55. doi:10.1007/s00251-001-0376-x. PMID 11797098. S2CID 12387932.
- Haruta H, Kato A, Todokoro K (april 2001). "Isolation of a novel interleukin-1-inducible nuclear protein bearing ankyrin-repeat motifs". The Journal of Biological Chemistry. 276 (16): 12485–8. doi:10.1074/jbc.C100075200. PMID 11278262.
- Yamazaki S, Muta T, Takeshige K (juli 2001). "A novel IkappaB protein, IkappaB-zeta, induced by proinflammatory stimuli, negatively regulates nuclear factor-kappaB in the nuclei". The Journal of Biological Chemistry. 276 (29): 27657–62. doi:10.1074/jbc.M103426200. PMID 11356851.
- Kitamura H, Kanehira K, Shiina T, Morimatsu M, Jung BD, Akashi S, Saito M (maj 2002). "Bacterial lipopolysaccharide induces mRNA expression of an IkappaB MAIL through toll-like receptor 4". The Journal of Veterinary Medical Science. 64 (5): 419–22. doi:10.1292/jvms.64.419. PMID 12069074.
- Kitamura H, Matsushita Y, Iwanaga T, Mori K, Kanehira K, Fujikura D, Morimatsu M, Saito M (mart 2003). "Bacterial lipopolysaccharide-induced expression of the IkappaB protein MAIL in B-lymphocytes and macrophages". Archives of Histology and Cytology. 66 (1): 53–62. doi:10.1679/aohc.66.53. PMID 12703554.
- Shiina T, Konno A, Oonuma T, Kitamura H, Imaoka K, Takeda N, Todokoro K, Morimatsu M (decembar 2004). "Targeted disruption of MAIL, a nuclear IkappaB protein, leads to severe atopic dermatitis-like disease". The Journal of Biological Chemistry. 279 (53): 55493–8. doi:10.1074/jbc.M409770200. PMID 15491998.
- Ito T, Morimatsu M, Oonuma T, Shiina T, Kitamura H, Syuto B (novembar 2004). "Transcriptional regulation of the MAIL gene in LPS-stimulated RAW264 mouse macrophages". Gene. 342 (1): 137–43. doi:10.1016/j.gene.2004.07.032. PMID 15527973.
- Yamamoto M, Yamazaki S, Uematsu S, Sato S, Hemmi H, Hoshino K, Kaisho T, Kuwata H, Takeuchi O, Takeshige K, Saitoh T, Yamaoka S, Yamamoto N, Yamamoto S, Muta T, Takeda K, Akira S (juli 2004). "Regulation of Toll/IL-1-receptor-mediated gene expression by the inducible nuclear protein IkappaBzeta". Nature. 430 (6996): 218–22. doi:10.1038/nature02738. PMID 15241416. S2CID 4384768.
- Yamaji D, Kitamura H, Kimura K, Matsushita Y, Okada H, Shiina T, Morimatsu M, Saito M (april 2004). "Cloning of bovine MAIL and its mRNA expression in white blood cells of Holstein cows". Veterinary Immunology and Immunopathology. 98 (3–4): 175–84. doi:10.1016/j.vetimm.2003.12.004. PMID 15010226.
- Yamazaki S, Muta T, Matsuo S, Takeshige K (januar 2005). "Stimulus-specific induction of a novel nuclear factor-kappaB regulator, IkappaB-zeta, via Toll/Interleukin-1 receptor is mediated by mRNA stabilization". The Journal of Biological Chemistry. 280 (2): 1678–87. doi:10.1074/jbc.M409983200. PMID 15522867.
- Motoyama M, Yamazaki S, Eto-Kimura A, Takeshige K, Muta T (mart 2005). "Positive and negative regulation of nuclear factor-kappaB-mediated transcription by IkappaB-zeta, an inducible nuclear protein". The Journal of Biological Chemistry. 280 (9): 7444–51. doi:10.1074/jbc.M412738200. PMID 15618216.
- Cowland JB, Muta T, Borregaard N (maj 2006). "IL-1beta-specific up-regulation of neutrophil gelatinase-associated lipocalin is controlled by IkappaB-zeta". Journal of Immunology. 176 (9): 5559–66. doi:10.4049/jimmunol.176.9.5559. PMID 16622025.
- Oonuma T, Morimatsu M, Ochiai K, Iwanaga T, Hashizume K (mart 2007). "Role of NF-kappaB in constitutive expression of MAIL in epidermal keratinocytes". The Journal of Veterinary Medical Science. 69 (3): 279–84. doi:10.1292/jvms.69.279. PMID 17409644.
- Matsuo S, Yamazaki S, Takeshige K, Muta T (august 2007). "Crucial roles of binding sites for NF-kappaB and C/EBPs in IkappaB-zeta-mediated transcriptional activation". The Biochemical Journal. 405 (3): 605–15. doi:10.1042/BJ20061797. PMC 2267307. PMID 17447895.