CXXC5 explained

CXXC-type zinc finger protein 5 is a protein that is encoded by the CXXC5 gene in humans.^{[1] [2] [3] [4]}

As indicated by its name, the CXXC5 plays a role as a transcription factor in the nucleus of cells, and involved in myelopoiesis, endothelial differentiation, vessel formation, and oligodendrocyte differentiation.^{[5] [6]}

The CXXC5 is also characterized as a negative feedback regulator of the Wnt/β-catenin signaling pathway functioning by direct interaction with the Dishevelled (Dvl) protein in the cytosol.^{[7] [8] [9]} The cytosolic overexpression of CXXC5 was induced by several pathophysiological conditions, such as osteoporosis, alopecia, senescence of growth plate, cutaneous wound, and restoration of the suppressed Wnt/β-catenin signaling by blockade of its Dvl binding function improved the pathological features as observed in Cxxc5^-/- mice.^[10] These results indicate that the Dvl binding with cytosolic CXXC5 could be a target for the development of agents for treating alopecia, acute wound, and short stature in childhood and adolescence, which exhibit suppressed Wnt/β-catenin signaling by cytosolic CXXC5 overexpression of the responsible tissue cells.^[11] The CXXC5-Dvl protein-protein interaction (PPI) as a target for development of agents in hair loss or acute wound was also confirmed by construction and testing the function of PTD-DBM, a peptide inhibiting the CXXC5-Dvl PPIl.

The improvement of abnormalities by the CXXC5-Dvl PPI inhibitor is attributed to restoration of damaged tissues by activating the stem cells through restorative activation of the suppressed Wnt/β-catenin signaling and its target genes involving regeneration.

Further reading

• Rual JF, Venkatesan K, Hao T, Hirozane-Kishikawa T, Dricot A, Li N, Berriz GF, Gibbons FD, Dreze M, Ayivi-Guedehoussou N, Klitgord N, Simon C, Boxem M, Milstein S, Rosenberg J, Goldberg DS, Zhang LV, Wong SL, Franklin G, Li S, Albala JS, Lim J, Fraughton C, Llamosas E, Cevik S, Bex C, Lamesch P, Sikorski RS, Vandenhaute J, Zoghbi HY, Smolyar A, Bosak S, Sequerra R, Doucette-Stamm L, Cusick ME, Hill DE, Roth FP, Vidal M . Towards a proteome-scale map of the human protein-protein interaction network . Nature . 437 . 7062 . 1173–8 . October 2005 . 16189514 . 10.1038/nature04209 . 2005Natur.437.1173R . 4427026 .
• Colland F, Jacq X, Trouplin V, Mougin C, Groizeleau C, Hamburger A, Meil A, Wojcik J, Legrain P, Gauthier JM . Functional proteomics mapping of a human signaling pathway . Genome Research . 14 . 7 . 1324–32 . July 2004 . 15231748 . 442148 . 10.1101/gr.2334104 .
• Matsuda A, Suzuki Y, Honda G, Muramatsu S, Matsuzaki O, Nagano Y, Doi T, Shimotohno K, Harada T, Nishida E, Hayashi H, Sugano S . Large-scale identification and characterization of human genes that activate NF-kappaB and MAPK signaling pathways . Oncogene . 22 . 21 . 3307–18 . May 2003 . 12761501 . 10.1038/sj.onc.1206406 . free .
• Yu W, Andersson B, Worley KC, Muzny DM, Ding Y, Liu W, Ricafrente JY, Wentland MA, Lennon G, Gibbs RA . Large-scale concatenation cDNA sequencing . Genome Research . 7 . 4 . 353–8 . April 1997 . 9110174 . 139146 . 10.1101/gr.7.4.353 .
• Andersson B, Wentland MA, Ricafrente JY, Liu W, Gibbs RA . A "double adaptor" method for improved shotgun library construction . Analytical Biochemistry . 236 . 1 . 107–13 . April 1996 . 8619474 . 10.1006/abio.1996.0138 .

External links

• • GRCh38: Ensembl release 89: ENSG00000171604 - Ensembl, May 2017
• GRCm38: Ensemble release 89: ENSMUSG00000046668 - Ensembl, May 2017
• "Human PubMed Reference" National Center for Biotechnology Information, U.S. National Library of Medicine.
• "Human PubMed Reference" National Center for Biotechnology Information, U.S. National Library of Medicine.

Notes and References

1. Zhang QH, Ye M, Wu XY, Ren SX, Zhao M, Zhao CJ, Fu G, Shen Y, Fan HY, Lu G, Zhong M, Xu XR, Han ZG, Zhang JW, Tao J, Huang QH, Zhou J, Hu GX, Gu J, Chen SJ, Chen Z . Cloning and functional analysis of cDNAs with open reading frames for 300 previously undefined genes expressed in CD34+ hematopoietic stem/progenitor cells . Genome Research . 10 . 10 . 1546–60 . October 2000 . 11042152 . 310934 . 10.1101/gr.140200 .
2. Andersson T, Södersten E, Duckworth JK, Cascante A, Fritz N, Sacchetti P, Cervenka I, Bryja V, Hermanson O . CXXC5 is a novel BMP4-regulated modulator of Wnt signaling in neural stem cells . The Journal of Biological Chemistry . 284 . 6 . 3672–81 . February 2009 . 19001364 . 10.1074/jbc.M808119200 . free .
3. Pendino F, Nguyen E, Jonassen I, Dysvik B, Azouz A, Lanotte M, Ségal-Bendirdjian E, Lillehaug JR . Functional involvement of RINF, retinoid-inducible nuclear factor (CXXC5), in normal and tumoral human myelopoiesis . Blood . 113 . 14 . 3172–81 . April 2009 . 19182210 . 10.1182/blood-2008-07-170035 . free .
4. Web site: Entrez Gene: CXXC5 CXXC finger 5.
5. Kim HY, Yoon JY, Yun JH, Cho KW, Lee SH, Rhee YM, Jung HS, Lim HJ, Lee H, Choi J, Heo JN, Lee W, No KT, Min D, Choi KY . CXXC5 is a negative-feedback regulator of the Wnt/β-catenin pathway involved in osteoblast differentiation . Cell Death and Differentiation . 22 . 6 . 912–20 . June 2015 . 25633194 . 10.1038/cdd.2014.238. 4423189 . free .
6. Kim HY, Yang DH, Shin SW, Kim MY, Yoon JH, Kim S, Park HC, Kang DW, Min D, Hur MW, Choi KY . CXXC5 is a transcriptional activator of Flk-1 and mediates bone morphogenic protein-induced endothelial cell differentiation and vessel formation . FASEB Journal . 28 . 2 . 615–26 . February 2014 . 24136587 . 10.1096/fj.13-236216 . free . 23959096 .
7. Lee SH, Kim MY, Kim HY, Lee YM, Kim H, Nam KA, Roh MR, Min D, Chung KY, Choi KY . The Dishevelled-binding protein CXXC5 negatively regulates cutaneous wound healing . The Journal of Experimental Medicine . 212 . 7 . 1061–80 . June 2015 . 26056233 . 10.1084/jem.20141601 . 4493411 . free .
8. Kim HY, Choi S, Yoon JH, Lim HJ, Lee H, Choi J, Ro EJ, Heo JN, Lee W, No KT, Choi KY . Small molecule inhibitors of the Dishevelled-CXXC5 interaction are new drug candidates for bone anabolic osteoporosis therapy . EMBO Molecular Medicine . 8 . 4 . 375–87 . April 2016 . 26941261 . 10.15252/emmm.201505714 . 4818757 . free .
9. Lee SH, Seo SH, Lee DH, Pi LQ, Lee WS, Choi KY . Targeting of CXXC5 by a Competing Peptide Stimulates Hair Regrowth and Wound–Induced Hair Neogenesis . The Journal of Investigative Dermatology . 137 . 11 . 2260–2269 . November 2017 . 28595998 . 10.1016/j.jid.2017.04.038 . free .
10. Choi S, Kim HY, Cha PH, Seo SH, Lee C, Choi Y, Shin W, Heo Y, Han G, Lee W, Choi KY . CXXC5 mediates growth plate senescence and is a target for enhancement of longitudinal bone growth . Life Science Alliance . 2 . 2 . e201800254 . April 2019 . 30971423 . 10.26508/lsa.201800254 . 6458850 . free .
11. Choi S, Kim HY, Cha PH, Seo SH, Lee C, Choi Y, Shin W, Heo Y, Han G, Lee W, Choi KY . CXXC5 mediates growth plate senescence and is a target for enhancement of longitudinal bone growth . Life Science Alliance . 2 . 2 . e201800254 . April 2019 . 30971423 . 10.26508/lsa.201800254 . 6458850 . free .