MZB1
Ćelijskospecifični protein marginalne zone B i B1 jest protein koji je kod ljudi kodiran genom MZB1 sa hromosoma 5.[5]
Povezujući ove zone sa kaspazama, u jednom radu iz 2001., navodi se da one imaju važnu ulogu u regulaciji apoptotskih signalnih puteva. Objaviliili su podatke o kloniranju, dvohibridnim sistemom kvasca, s dominantnom negativnom kaspazom-2 kao "mamcem", proapoptotske molekule zvane proapoptotski protein kaspaznog adaptora (PACAP), kodirane otvorenim okvirom čitanja od 372 parova baza. Vezivanje ovog novog proteina za kaspazu-2 (kasp-2) potvrđeno je u dva hibridna testa kvasca, in vitro i in vivo. Zaključena aminokiselinska sekvenca otkrila je homologiju funkcionalnih motiva, uključujući ATP i mjesta vezanja citohroma C. iRNK bila je široko eksprimirana u većini ljudskih tkiva; u transficiranim ćelijamama, bio je difuzno eksprimiran u citoplazmi. Studije vezivanja sa rekombinantnim proteinom pokazale su specifično vezivanje za casp -2 i casp –9, ali ne i za casp –3, –4,–7 ili –8 u ćelijskim ekstraktima. Eksperimenti kotransfekcije pokazali su da se protrin PACAP veže za casp –2 i –9 u ćelijama 293T. Osim toga, studije sa skraćenim PACAP-om pokazale su potrebu za ostacima 39-72 PACAP-a za specifično vezivanje za casp-2 i –9.
Prolazna transfekcija PACAP-a u 293T ćelije ljudskog bubrega i fibroblaste pacova pokrenula je apoptozu nakon 24 sata, što je barem djelimično spriječeno inhibitorom enzima sličnih casp-3. Transfekcija PACAP a u ljudske B-ćelijske linije korištenjem retrovirusnog sistema, također je pokrenula apoptotsku ćelijsku smrt. Osim toga, transkripcija PACAP-a u primarnim ljudskim B-ćelijama dramatično je smanjena rano nakon ćelijske aktivacije pomoću CD40L i Staphylococcus aureus i značajno povećana kao ćelijska apoptoza. Ovi nalazi identifikuju novi proapoptotski protein adaptora kaspaze.[6]
Aminokiselinska sekvenca
urediDužina polipeptidnog lanca je 189 aminokiselina, а molekulska težina 20.694 Da.[7]
| 10 | 20 | 30 | 40 | 50 | ||||
|---|---|---|---|---|---|---|---|---|
| MRLSLPLLLL | LLGAWAIPGG | LGDRAPLTAT | APQLDDEEMY | SAHMPAHLRC | ||||
| DACRAVAYQM | WQNLAKAETK | LHTSNSGGRR | ELSELVYTDV | LDRSCSRNWQ | ||||
| DYGVREVDQV | KRLTGPGLSE | GPEPSISVMV | TGGPWPTRLS | RTCLHYLGEF | ||||
| GEDQIYEAHQ | QGRGALEALL | CGGPQGACSE | KVSATREEL |
Reference
uredi- ^ a b c GRCh38: Ensembl release 89: ENSG00000170476 - Ensembl, maj 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000024353 - 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.
- ^ "Entrez Gene: Marginal zone B and B1 cell-specific protein".
- ^ Bonfoco E., Li E., Kolbinger F., Cooper N.R.J. (2001): Characterization of a novel proapoptotic caspase-2- and caspase-9-binding protein. Biol. Chem. 276:29242-29250. PubMed [Europe PMC]
- ^ "UniProt, Q8WU39" (jezik: engleski). Pristupljeno 17. 10. 2021.
Dopunska literatura
uredi- Zhang H, Chen S, Huang L (maj 2012). "[Proteomics-based identification of proapoptotic caspase adapter protein as a novel serum marker of non-small cell lung cancer]". Zhongguo Fei AI Za Zhi = Chinese Journal of Lung Cancer. 15 (5): 287–93. doi:10.3779/j.issn.1009-3419.2012.05.07. PMC 6000130. PMID 22613335.
- Vaudry D, Rousselle C, Basille M, Falluel-Morel A, Pamantung TF, Fontaine M, Fournier A, Vaudry H, Gonzalez BJ (april 2002). "Pituitary adenylate cyclase-activating polypeptide protects rat cerebellar granule neurons against ethanol-induced apoptotic cell death". Proceedings of the National Academy of Sciences of the United States of America. 99 (9): 6398–403. Bibcode:2002PNAS...99.6398V. doi:10.1073/pnas.082112699. PMC 122960. PMID 11972030.
- Bonfoco E, Li E, Kolbinger F, Cooper NR (august 2001). "Characterization of a novel proapoptotic caspase-2- and caspase-9-binding protein". The Journal of Biological Chemistry. 276 (31): 29242–50. doi:10.1074/jbc.M100684200. PMID 11350957.
- Katoh M, Katoh M (juli 2003). "MGC29506 gene, frequently down-regulated in intestinal-type gastric cancer, encodes secreted-type protein with conserved cysteine residues". International Journal of Oncology. 23 (1): 235–41. PMID 12792799.
- Zhang H, Chen X, Sairam MR (septembar 2011). "Novel hormone-regulated genes in visceral adipose tissue: cloning and identification of proinflammatory cytokine-like mouse and human MEDA-7: implications for obesity, insulin resistance and the metabolic syndrome". Diabetologia. 54 (9): 2368–80. doi:10.1007/s00125-011-2212-7. PMID 21688198.
- Flach H, Rosenbaum M, Duchniewicz M, Kim S, Zhang SL, Cahalan MD, Mittler G, Grosschedl R (novembar 2010). "Mzb1 protein regulates calcium homeostasis, antibody secretion, and integrin activation in innate-like B cells". Immunity. 33 (5): 723–35. doi:10.1016/j.immuni.2010.11.013. PMC 3125521. PMID 21093319.
- Shimizu Y, Meunier L, Hendershot LM (oktobar 2009). "pERp1 is significantly up-regulated during plasma cell differentiation and contributes to the oxidative folding of immunoglobulin". Proceedings of the National Academy of Sciences of the United States of America. 106 (40): 17013–8. Bibcode:2009PNAS..10617013S. doi:10.1073/pnas.0811591106. PMC 2761359. PMID 19805157.
- van Anken E, Pena F, Hafkemeijer N, Christis C, Romijn EP, Grauschopf U, Oorschot VM, Pertel T, Engels S, Ora A, Lástun V, Glockshuber R, Klumperman J, Heck AJ, Luban J, Braakman I (oktobar 2009). "Efficient IgM assembly and secretion require the plasma cell induced endoplasmic reticulum protein pERp1". Proceedings of the National Academy of Sciences of the United States of America. 106 (40): 17019–24. Bibcode:2009PNAS..10617019V. doi:10.1073/pnas.0903036106. PMC 2761347. PMID 19805154.
- Matsumura S, Imoto I, Kozaki K, Matsui T, Muramatsu T, Furuta M, Tanaka S, Sakamoto M, Arii S, Inazawa J (juli 2012). "Integrative array-based approach identifies MZB1 as a frequently methylated putative tumor suppressor in hepatocellular carcinoma". Clinical Cancer Research. 18 (13): 3541–51. doi:10.1158/1078-0432.CCR-11-1007. PMID 22573353.