CIDEB
Inducirajući efektor b ćelijske smrti sličan DFFA, znan i kao CIDEB, je ljudski gen.[5][6][7]
Nedavno je CIDEB nokaut-miševa generiran tehnikom homologne rekombinacije. CIDE nulti miševi pokazuju smanjenje lipogeneze. CIDEB nokaut- miševi otporni su na gojaznost i jetrenu steatozu izazvanu ishranom sa puno masnoća. Pored toga, nulti miševi CIDEB također imaju poboljšanu osetljivost na insulin i pojačan metabolizam jetrene oksidacije masnih kiselina i cijelog tela.[8]
Lugovskoy et al. (1999) izvijestili su o strukturi konzerviranog N-terminalnog domena (CIDE-N) ljudskog CIDEB. Pokazali su da CIDE-N domen CIDEB komunicira sa CIDE-N domenima i DFF40 i DFF45. Vezni epitopi bili su slični i locirani u visoko nabijenoj bipolarnoj površini CIDEB-a. Nadalje, pokazali su da CIDE-N domen CIDEB regulira enzimsku aktivnost kompleksa DFF40 / DFF45 in vitro.[9]
Aminokiselinska sekvenca[uredi | uredi izvor]
Dužina polipeptidnog lanca je 219 aminokiselina, a molekulska težina 24.678 Da.[10]
| 10 | 20 | 30 | 40 | 50 | ||||
|---|---|---|---|---|---|---|---|---|
| MEYLSALNPS | DLLRSVSNIS | SEFGRRVWTS | APPPQRPFRV | CDHKRTIRKG | ||||
| LTAATRQELL | AKALETLLLN | GVLTLVLEED | GTAVDSEDFF | QLLEDDTCLM | ||||
| VLQSGQSWSP | TRSGVLSYGL | GRERPKHSKD | IARFTFDVYK | QNPRDLFGSL | ||||
| NVKATFYGLY | SMSCDFQGLG | PKKVLRELLR | WTSTLLQGLG | HMLLGISSTL | ||||
| RHAVEGAEQW | QQKGRLHSY |
- Simboli
C: Cistein
D: Asparaginska kiselina
E: Glutaminska kiselina
F: Fenilalanin
G: Glicin
H: Histidin
I: Izoleucin
K: Lizin
L: Leucin
M: Metionin
N: Asparagin
P: Prolin
Q: Glutamin
R: Arginin
S: Serin
T: Treonin
V: Valin
W: Triptofan
Y: Tirozin
Kloniranje i ekspresija[uredi | uredi izvor]
Inohara et al. (1998) izvijestili su o identifikaciji i karakterizaciji dva sisarska gena, koje su nazvali CIDEA i CIDEB (efektori A i B slični DFFA-u koji induciraju ćelijsku smrt), kodirajući visoko povezane proteine s homologijom u N-terminalnom području DFF45, podjedinici faktora fragmentacije DNK (DFF) koja se za vrijeme apoptoze razlaže kaspazom-3 . Utvrđeno je da CIDEA i CIDEB aktiviraju apoptozu u ćelijama sisara, a to je inhibirano DFF45, ali ne i inhibitorima kaspaze. Izražavanje CIDEA-om inducirane fragmentacije DNK u T-ćelija]]ma 293, što je također inhibirao DFF45; to dalje sugerira da DFF45 inhibira apoptotske aktivnosti CIDE. Pored CIDEA i CIDEB sisara, Inohara et al. ](1998) identificirali su DREP1, [[homolog roda Drosophila DFF45, koji bi mogao inhibirati apoptozu posredovanu CIDEA.
Analiza mutacija otkrila je da je C-terminalna regija CIDEA neophodna i dovoljna za ubijanje ćelija, dok je region s homologijom DFF45 na N-terminalu potreban da DFF45 inhibira apoptozu izazvanu CIDEA-om. Apoptoza posredovana CD95/Fas poboljšana je CIDE-ima, ali inhibirana DFF45-om. Ova ispitivanja sugeriraju da je DFF45 evolucijski konzerviran i podrazumijeva CIDE kao efektore koji inhibiraju DFF45 za promoviranje ćelijske smrti i fragmentacije DNK.[11]
Reference[uredi | uredi izvor]
- ^ a b c ENSG00000285199 GRCh38: Ensembl release 89: ENSG00000136305, ENSG00000285199 - Ensembl, maj 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000022219 - 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: CIDEB cell death-inducing effector b".
- ^ Ye, Jing; Zhong Li, John; Liu, Yang; Li, Xuanhe; Yang, Tianshu; Ma, Xiaodong; Li, Qing; Yao, Zemin; Li, Peng (2009). "Cideb, an ER- and Lipid Droplet-Associated Protein, Mediates VLDL Lipidation and Maturation by Interacting with Apolipoprotein B." Cell Metabolism. 9 (2): 177–190. doi:10.1016/j.cmet.2008.12.013. PMID 19187774.
- ^ Li, JZ; Lei, Y; Wang, Y; Zhang, Y; Ye, J; Xia, X; Pan, X; Li, P (maj 2010). "Control of cholesterol biosynthesis, uptake and storage in hepatocytes by Cideb". Biochim Biophys Acta. 1801 (5): 577–86. doi:10.1016/j.bbalip.2010.01.012. PMID 20123130.
- ^ Zhong Li, John; Ye, Jing; Xue, Bofu; Qi, Jingzong; Zhang, Jing; Zhou, Zhihong; Li, Qing; Wen, Zilong; Li, Peng (2007). /cgi/content/short/56/10/2523 "Cideb regulates diet-induced obesity, liver steatosis and insulin sensitivity by controlling lipogeneis and fatty acid oxidation" Provjerite vrijednost parametra
|url=(pomoć). Diabetes. 56 (10): 2523–2532. doi:10.2337/db07-0040. PMID 17646209. - ^ Lugovskoy, A. A., Zhou, P., Chou, J. J., McCarty, J. S., Li, P., Wagner, G. Solution structure of the CIDE-N domain of CIDE-B and a model for CIDE-N/CIDE-N interactions in the DNA fragmentation pathway of apoptosis. Cell 99: 747-755, 1999. PubMed: 10619428
- ^ "UniProt, Q9UHD4". Pristupljeno 22. 7. 2021.
- ^ Inohara, N., Koseki, T., Chen, S., Wu, X., Nunez, G. CIDE, a novel family of cell death activators with homology to the 45 kDa subunit of the DNA fragmentation factor. EMBO J. 17: 2526-2533, 1998. PubMed: 9564035
Dopunska literatura[uredi | uredi izvor]
- Inohara N, Koseki T, Chen S, et al. (1998). "CIDE, a novel family of cell death activators with homology to the 45 kDa subunit of the DNA fragmentation factor". EMBO J. 17 (9): 2526–33. doi:10.1093/emboj/17.9.2526. PMC 1170594. PMID 9564035.
- Lugovskoy AA, Zhou P, Chou JJ, et al. (2000). "Solution structure of the CIDE-N domain of CIDE-B and a model for CIDE-N/CIDE-N interactions in the DNA fragmentation pathway of apoptosis". Cell. 99 (7): 747–55. doi:10.1016/S0092-8674(00)81672-4. PMID 10619428.
- Chen Z, Guo K, Toh SY, et al. (2000). "Mitochondria localization and dimerization are required for CIDE-B to induce apoptosis". J. Biol. Chem. 275 (30): 22619–22. doi:10.1074/jbc.C000207200. PMID 10837461.
- Liang L, Zhao M, Xu Z, et al. (2003). "Molecular cloning and characterization of CIDE-3, a novel member of the cell-death-inducing DNA-fragmentation-factor (DFF45)-like effector family". Biochem. J. 370 (Pt 1): 195–203. doi:10.1042/BJ20020656. PMC 1223158. PMID 12429024.
- Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932.
- Erdtmann L, Franck N, Lerat H, et al. (2003). "The hepatitis C virus NS2 protein is an inhibitor of CIDE-B-induced apoptosis". J. Biol. Chem. 278 (20): 18256–64. doi:10.1074/jbc.M209732200. PMID 12595532.
- Ota T, Suzuki Y, Nishikawa T, et al. (2004). "Complete sequencing and characterization of 21,243 full-length human cDNAs". Nat. Genet. 36 (1): 40–5. doi:10.1038/ng1285. PMID 14702039.
- Gerhard DS, Wagner L, Feingold EA, et al. (2004). "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)". Genome Res. 14 (10B): 2121–7. doi:10.1101/gr.2596504. PMC 528928. PMID 15489334.
- Da L, Li D, Yokoyama KK, et al. (2006). "Dual promoters control the cell-specific expression of the human cell death-inducing DFF45-like effector B gene". Biochem. J. 393 (Pt 3): 779–88. doi:10.1042/BJ20051027. PMC 1360731. PMID 16248853.
- Li JZ, Lei Y, Wang Y, Zhang Y, Ye J, Xia X, Pan X, Li P, et al. (2010). "Control of cholesterol biosynthesis, uptake and storage in hepatocytes by Cideb". Biochim Biophys Acta. 1801 (Pt 5): 577–586. doi:10.1016/j.bbalip.2010.01.012. PMID 20123130.