LAPTM4B
Lizosomno-pridruženi transmembranski protein 4B je protein koji je kod ljudi kodiran genom LAPTM4B.[5]
Protein LAPTM4B sadrži lizosomno lokaliziran motiv i nalazi se na kasnim endosomima i lizosomima.
Aminokiselinska sekvenca uredi
Dužina polipeptidnog lanca je 370 aminokiselina, а molekulska težina 41.146 Da.[6]
| 10 | 20 | 30 | 40 | 50 | ||||
|---|---|---|---|---|---|---|---|---|
| MELHERPDER | RKARTSTQGR | LGDWRRVHAD | GFTHRVLGAP | AAAWSSSSWL | ||||
| EPAMTSRTRV | TWPSPPRPLP | VPAAAAVAFG | AKGTDPAEAR | SSRGIEEAGP | ||||
| RAHGRAGREP | ERRRSRQQRR | GGLQARRSTL | LKTCARARAT | APGAMKMVAP | ||||
| WTRFYSNSCC | LCCHVRTGTI | LLGVWYLIIN | AVVLLILLSA | LADPDQYNFS | ||||
| SSELGGDFEF | MDDANMCIAI | AISLLMILIC | AMATYGAYKQ | RAAWIIPFFC | ||||
| YQIFDFALNM | LVAITVLIYP | NSIQEYIRQL | PPNFPYRDDV | MSVNPTCLVL | ||||
| IILLFISIIL | TFKGYLISCV | WNCYRYINGR | NSSDVLVYVT | SNDTTVLLPP | ||||
| YDDATVNGAA | KEPPPPYVSA |
Klinički značaj uredi
Povećana ekspresija LAPTM4B nađena je u karcinomima dojke, jetre, pluća, jajnika, materice i želuca. Povišeni nivo LAPTM4B doprinosi rezistenciji na hemoterapiju kod raka dojke. Utvrđeno je da nadekspresija LAPTM4B uzrokuje rezistenciju na antracikline (doksorubicin, daunorubicin i epirubicin), zadržavanjem lijeka u citoplazmi i smanjenjem jedarne lokalizacije lijekova i lijekovima izazvanih oštećenje DNK.[7]
U 2011., ista grupa izvijestila je da LAPTM4B također promovira autofagiju, mehanizam preživljavanja ćelija posredovan lizosomima. LAPTM4B podstiče autofagiju i čini tumorske ćelije otpornima na metabolički i genotoksični stres, te rezultira bržim rastom tumora.[8]
Na temelju ovih nalaza, LAPTM4B se može koristiti kao terapijski cilj za sprječavanje rezistencije na hemoterapiju ili kao marker za identifikaciju pacijenata koji neće imati koristi od antraciklina.[7]
Reference uredi
- ^ a b c GRCh38: Ensembl release 89: ENSG00000104341 - Ensembl, maj 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000022257 - 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: LAPTM4B lysosomal associated protein transmembrane 4 beta".
- ^ "UniProt, Q86VI4" (jezik: engleski). Pristupljeno 19. 9. 2021.
- ^ a b Li Y, Zou L, Li Q, Haibe-Kains B, Tian R, Li Y, Desmedt C, Sotiriou C, Szallasi Z, Iglehart JD, Richardson AL, Wang ZC (februar 2010). "Amplification of LAPTM4B and YWHAZ contributes to chemotherapy resistance and recurrence of breast cancer". Nat. Med. 16 (2): 214–8. doi:10.1038/nm.2090. PMC 2826790. PMID 20098429.
- ^ Li Y, Zhang Q, Tian R, Wang Q, Zhao JJ, Iglehart JD, Wang ZC, Richardson AL (decembar 2011). "Lysosomal transmembrane protein LAPTM4B promotes autophagy and tolerance to metabolic stress in cancer cells". Cancer Res. 71 (24): 7481–9. doi:10.1158/0008-5472.CAN-11-0940. PMC 3261660. PMID 22037872.
Dopunska literatura uredi
- Hartley JL, Temple GF, Brasch MA (2001). "DNA cloning using in vitro site-specific recombination". Genome Res. 10 (11): 1788–95. doi:10.1101/gr.143000. PMC 310948. PMID 11076863.
- Wiemann S, Weil B, Wellenreuther R, et al. (2001). "Toward a catalog of human genes and proteins: sequencing and analysis of 500 novel complete protein coding human cDNAs". Genome Res. 11 (3): 422–35. doi:10.1101/gr.GR1547R. PMC 311072. PMID 11230166.
- 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.
- With S, Rice T, Salinas C, Auld V (2003). "Fire exit is a potential four transmembrane protein expressed in developing Drosophila glia". Genesis. 35 (3): 143–52. doi:10.1002/gene.10177. PMID 12640618. S2CID 29252213.
- Shao GZ, Zhou RL, Zhang QY, et al. (2003). "Molecular cloning and characterization of LAPTM4B, a novel gene upregulated in hepatocellular carcinoma". Oncogene. 22 (32): 5060–9. doi:10.1038/sj.onc.1206832. PMID 12902989.
- Liu XR, Zhou RL, Zhang QY, et al. (2004). "Structure analysis and expressions of a novel tetratransmembrane protein, lysosoma-associated protein transmembrane 4 beta associated with hepatocellular carcinoma". World J. Gastroenterol. 10 (11): 1555–9. doi:10.3748/wjg.v10.i11.1555. PMC 4572753. PMID 15162524.
- 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.
- Wiemann S, Arlt D, Huber W, et al. (2004). "From ORFeome to biology: a functional genomics pipeline". Genome Res. 14 (10B): 2136–44. doi:10.1101/gr.2576704. PMC 528930. PMID 15489336.
- Kasper G, Vogel A, Klaman I, et al. (2005). "The human LAPTM4b transcript is upregulated in various types of solid tumours and seems to play a dual functional role during tumour progression". Cancer Lett. 224 (1): 93–103. doi:10.1016/j.canlet.2004.10.004. PMID 15911104.
- Otsuki T, Ota T, Nishikawa T, et al. (2007). "Signal sequence and keyword trap in silico for selection of full-length human cDNAs encoding secretion or membrane proteins from oligo-capped cDNA libraries". DNA Res. 12 (2): 117–26. doi:10.1093/dnares/12.2.117. PMID 16303743.
- Mehrle A, Rosenfelder H, Schupp I, et al. (2006). "The LIFEdb database in 2006". Nucleic Acids Res. 34 (Database issue): D415–8. doi:10.1093/nar/gkj139. PMC 1347501. PMID 16381901.
- Maeda K, Horikoshi T, Nakashima E, et al. (2007). "MATN and LAPTM are parts of larger transcription units produced by intergenic splicing: intergenic splicing may be a common phenomenon". DNA Res. 12 (5): 365–72. doi:10.1093/dnares/dsi017. PMID 16769693.
- Liu Y, Zhang QY, Qian N, Zhou RL (2007). "Relationship between LAPTM4B gene polymorphism and susceptibility of gastric cancer". Ann. Oncol. 18 (2): 311–6. doi:10.1093/annonc/mdl394. PMID 17074969.