Epiplakin
Epiplakin is a large cytoplasmic protein that is encoded by the EPPK1 gene in humans. Epiplakin was first identified as an autoantigen.[4]
Discovery
The initial discovery of Epiplakin came from a patient who had a rare autoimmune skin disease that caused blistering at the junction of the epidermis and dermis. After closer examination, scientists saw that the patient's blood had contained autoantibodies that reacted with an unknown protein in the epidermis. The unknown protein was almost entirely made of repeated plakin domains.[4]
Subcellular distribution
The peptide recognition domain of epiplakin is able to bind to keratins in vitro; however, in cells the epiplakin associates with keratin intermediate filaments networks only under conditions in which cellular stress is absent. Otherwise, epiplakin remains universally cytoplasmic and not bound to the intermediate filaments.
Structure
Human epiplakin contains 13 peptide recognition domains (PRDs) and have a total size of about 725 kDa. Unlike plakins, they lack an N-terminal actin-binding domain.[5][4]
Function
Epiplakin's role in maintaining keratin intermediate filament organization suggests that dysregulation of epiplakin expression or function may contribute to epithelial fragility or altered wound-healing responses, as indicated by accelerated wound closure observed in epiplakin-depleted corneal epithelial cells.
Clinical significance
Cancer
Scientists have examined EPPK1 expression in multiple types/forms of cancers (bladder, lung, colon, etc.). Various studies show that altered Epiplakin levels in tumor tissues show correlation with tumor progression pathways.[6]
References
- ^ a b c GRCh38: Ensembl release 89: ENSG00000261150 – Ensembl, May 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.
- ^ a b c Fujiwara S, Takeo N, Otani Y, Parry DA, Kunimatsu M, Lu R, et al. (April 2001). "Epiplakin, a novel member of the Plakin family originally identified as a 450-kDa human epidermal autoantigen. Structure and tissue localization". The Journal of Biological Chemistry. 276 (16): 13340–13347. doi:10.1074/jbc.M011386200. PMID 11278896.
- ^ Spazierer D, Fuchs P, Pröll V, Janda L, Oehler S, Fischer I, et al. (August 2003). "Epiplakin gene analysis in mouse reveals a single exon encoding a 725-kDa protein with expression restricted to epithelial tissues". The Journal of Biological Chemistry. 278 (34): 31657–31666. doi:10.1074/jbc.M303055200. PMID 12791695.
- ^ Shimura S, Matsumoto K, Shimizu Y, Mochizuki K, Shiono Y, Hirano S, et al. (October 2021). "Serum Epiplakin Might Be a Potential Serodiagnostic Biomarker for Bladder Cancer". Cancers. 13 (20): 5150. doi:10.3390/cancers13205150. PMC 8534213. PMID 34680299.
Further reading
- Fujiwara S, Kohno K, Iwamatsu A, Naito I, Shinkai H (May 1996). "Identification of a 450-kDa human epidermal autoantigen as a new member of the plectin family". The Journal of Investigative Dermatology. 106 (5): 1125–1130. doi:10.1111/1523-1747.ep12340171. PMID 8618051.
- Blagoev B, Kratchmarova I, Ong SE, Nielsen M, Foster LJ, Mann M (March 2003). "A proteomics strategy to elucidate functional protein-protein interactions applied to EGF signaling". Nature Biotechnology. 21 (3): 315–318. doi:10.1038/nbt790. PMID 12577067. S2CID 26838266.
- Gevaert K, Goethals M, Martens L, Van Damme J, Staes A, Thomas GR, et al. (May 2003). "Exploring proteomes and analyzing protein processing by mass spectrometric identification of sorted N-terminal peptides". Nature Biotechnology. 21 (5): 566–569. Bibcode:2003NatBi..21..566G. doi:10.1038/nbt810. PMID 12665801. S2CID 23783563.
- Spazierer D, Fuchs P, Pröll V, Janda L, Oehler S, Fischer I, et al. (August 2003). "Epiplakin gene analysis in mouse reveals a single exon encoding a 725-kDa protein with expression restricted to epithelial tissues". The Journal of Biological Chemistry. 278 (34): 31657–31666. doi:10.1074/jbc.M303055200. PMID 12791695.
- Takeo N, Wang W, Matsuo N, Sumiyoshi H, Yoshioka H, Fujiwara S (November 2003). "Structure and heterogeneity of the human gene for epiplakin (EPPK1)". The Journal of Investigative Dermatology. 121 (5): 1224–1226. doi:10.1046/j.1523-1747.2003.12550_5.x. PMID 14708632.
- Kim JE, Tannenbaum SR, White FM (2005). "Global phosphoproteome of HT-29 human colon adenocarcinoma cells". Journal of Proteome Research. 4 (4): 1339–1346. doi:10.1021/pr050048h. PMID 16083285.
- Nousiainen M, Silljé HH, Sauer G, Nigg EA, Körner R (April 2006). "Phosphoproteome analysis of the human mitotic spindle". Proceedings of the National Academy of Sciences of the United States of America. 103 (14): 5391–5396. Bibcode:2006PNAS..103.5391N. doi:10.1073/pnas.0507066103. PMC 1459365. PMID 16565220.
- Olsen JV, Blagoev B, Gnad F, Macek B, Kumar C, Mortensen P, et al. (November 2006). "Global, in vivo, and site-specific phosphorylation dynamics in signaling networks". Cell. 127 (3): 635–648. doi:10.1016/j.cell.2006.09.026. PMID 17081983. S2CID 7827573.
- Ewing RM, Chu P, Elisma F, Li H, Taylor P, Climie S, et al. (2007). "Large-scale mapping of human protein-protein interactions by mass spectrometry". Molecular Systems Biology. 3 (1) 89. doi:10.1038/msb4100134. PMC 1847948. PMID 17353931.