CXXC5

Last updated
CXXC5
Identifiers
Aliases CXXC5 , CF5, RINF, WID, HSPC195, CXXC finger protein 5
External IDs OMIM: 612752 MGI: 1914643 HomoloGene: 9517 GeneCards: CXXC5
Orthologs
SpeciesHumanMouse
Entrez

51523

67393

Ensembl

ENSG00000171604

ENSMUSG00000046668

UniProt

Q7LFL8

Q91WA4

RefSeq (mRNA)

NM_133687
NM_001357458
NM_001357459

RefSeq (protein)

NP_598448
NP_001344387
NP_001344388

Location (UCSC) Chr 5: 139.65 – 139.68 Mb Chr 18: 35.96 – 35.99 Mb
PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

CXXC-type zinc finger protein 5 is a protein that is encoded by the CXXC5 gene in humans. [5] [6] [7] [8]

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. [9] [10] [7]

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. [6] [9] [11] [12] [13] 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. [9] [12] [13] [14] 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] [13] [15] 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. [11] [13]

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.

Related Research Articles

The Wnt signaling pathways are a group of signal transduction pathways which begin with proteins that pass signals into a cell through cell surface receptors. The name Wnt is a portmanteau created from the names Wingless and Int-1. Wnt signaling pathways use either nearby cell-cell communication (paracrine) or same-cell communication (autocrine). They are highly evolutionarily conserved in animals, which means they are similar across animal species from fruit flies to humans.

<span class="mw-page-title-main">Catenin beta-1</span> Mammalian protein found in Homo sapiens

Catenin beta-1, also known as β-catenin (beta-catenin), is a protein that in humans is encoded by the CTNNB1 gene.

<span class="mw-page-title-main">CTNNBIP1</span> Protein-coding gene in the species Homo sapiens

Beta-catenin-interacting protein 1 is a protein that is encoded in humans by the CTNNBIP1 gene.

<span class="mw-page-title-main">AXIN1</span> Protein-coding gene in the species Homo sapiens

Axin-1 is a protein that in humans is encoded by the AXIN1 gene.

<span class="mw-page-title-main">DKK1</span> Protein-coding gene in the species Homo sapiens

Dickkopf-related protein 1 is a protein that in humans is encoded by the DKK1 gene.

<span class="mw-page-title-main">DVL1</span> Human protein and coding gene

Segment polarity protein dishevelled homolog DVL-1 is a protein that in humans is encoded by the DVL1 gene.

<span class="mw-page-title-main">Secreted frizzled-related protein 1</span> Protein-coding gene in the species Homo sapiens

Secreted frizzled-related protein 1, also known as SFRP1, is a protein which in humans is encoded by the SFRP1 gene.

<span class="mw-page-title-main">LRP6</span> Protein-coding gene in the species Homo sapiens

Low-density lipoprotein receptor-related protein 6 is a protein that in humans is encoded by the LRP6 gene. LRP6 is a key component of the LRP5/LRP6/Frizzled co-receptor group that is involved in canonical Wnt pathway.

<span class="mw-page-title-main">WNT3A</span> Protein-coding gene in the species Homo sapiens

Protein Wnt-3a is a protein that in humans is encoded by the WNT3A gene.

<span class="mw-page-title-main">HBP1</span> Protein-coding gene in the species Homo sapiens

HMG-box transcription factor 1, also known as HBP1, is a human protein.

<span class="mw-page-title-main">DVL2</span> Human protein and coding gene

Segment polarity protein dishevelled homolog DVL-2 is a protein that in humans is encoded by the DVL2 gene.

<span class="mw-page-title-main">DVL3</span> Protein-coding gene in the species Homo sapiens

Segment polarity protein dishevelled homolog DVL-3 is a protein that in humans is encoded by the DVL3 gene.

<span class="mw-page-title-main">Protein chibby homolog 1</span> Protein-coding gene in the species Homo sapiens

Protein chibby homolog 1 is a protein that in humans is encoded by the CBY1 gene.

<span class="mw-page-title-main">LBH (gene)</span> Protein-coding gene in the species Homo sapiens

The LBH gene is a highly conserved human gene that produces the LBH protein, a transcription co-factor in the Wnt/β-catenin pathway. Upon transcriptional activation of β-catenin, LBH goes on to act as a regulator of cell proliferation and differentiation through multiple transcriptional targets. The gene is located on the p arm of chromosome 2 and is roughly 28 kb long. Current ongoing studies are examining its role in developmental and oncological settings.

<span class="mw-page-title-main">R-spondin 1</span> Protein-coding gene in the species Homo sapiens

R-spondin-1 is a secreted protein that in humans is encoded by the RSPO1 gene, found on chromosome 1. In humans, it interacts with WNT4 in the process of female sex development. Loss of function can cause female to male sex reversal. Furthermore, it promotes canonical WNT/β catenin signaling.

<span class="mw-page-title-main">BCL9</span> Protein-coding gene in the species Homo sapiens

B-cell CLL/lymphoma 9 protein is a protein that in humans is encoded by the BCL9 gene.

<span class="mw-page-title-main">Dishevelled</span> Family of proteins

Dishevelled (Dsh) is a family of proteins involved in canonical and non-canonical Wnt signalling pathways. Dsh is a cytoplasmic phosphoprotein that acts directly downstream of frizzled receptors. It takes its name from its initial discovery in flies, where a mutation in the dishevelled gene was observed to cause improper orientation of body and wing hairs. There are vertebrate homologs in zebrafish, Xenopus (Xdsh), mice and humans. Dsh relays complex Wnt signals in tissues and cells, in normal and abnormal contexts. It is thought to interact with the SPATS1 protein when regulating the Wnt Signalling pathway.

<span class="mw-page-title-main">TCF7L1</span> Protein-coding gene in the species Homo sapiens

Transcription factor 7-like 1, also known as TCF7L1, is a human gene.

Kang-Yell Choi is a professor of biotechnology at Yonsei University, and has a joint appointment position as a CEO of CK Regeon Inc. in Seoul, Korea. He has been performing researches related to cellular signaling, especially for the Wnt/β-catenin pathway involving various pathophysiologies. Choi has been leading the Translational Research Center for Protein Function Control (TRCP), a Korean government supported drug development institute, as a director for 10 years. Choi has been carrying out R&D to develop agents controlling the Wnt/β-catenin signaling pathway. Choi's main interest is development of the agents to treat intractable diseases that suppress tissue regeneration system through overexpression of CXXC5 and subsequent suppression of the Wnt/β-catenin signaling.

Protein Transduction Domain-fused Dishevelled Binding Motif (PTD-DBM) is a man-made peptide which interacts with the mechanism of the hair loss linked endogenous protein, CXXC5, which is a negative feedback regulator of the Wnt/β-catenin pathway. Application of the peptide to bald laboratory mice resulted in new hair follicle growth.

References

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000171604 - Ensembl, May 2017
  2. 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000046668 - Ensembl, May 2017
  3. ↑ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ↑ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ↑ Zhang QH, Ye M, Wu XY, Ren SX, Zhao M, Zhao CJ, et al. (October 2000). "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. doi:10.1101/gr.140200. PMC   310934 . PMID   11042152.
  6. 1 2 Andersson T, Södersten E, Duckworth JK, Cascante A, Fritz N, Sacchetti P, et al. (February 2009). "CXXC5 is a novel BMP4-regulated modulator of Wnt signaling in neural stem cells". The Journal of Biological Chemistry. 284 (6): 3672–81. doi: 10.1074/jbc.M808119200 . PMID   19001364.
  7. 1 2 Pendino F, Nguyen E, Jonassen I, Dysvik B, Azouz A, Lanotte M, et al. (April 2009). "Functional involvement of RINF, retinoid-inducible nuclear factor (CXXC5), in normal and tumoral human myelopoiesis". Blood. 113 (14): 3172–81. doi: 10.1182/blood-2008-07-170035 . PMID   19182210.
  8. ↑ "Entrez Gene: CXXC5 CXXC finger 5".
  9. 1 2 3 Kim HY, Yoon JY, Yun JH, Cho KW, Lee SH, Rhee YM, et al. (June 2015). "CXXC5 is a negative-feedback regulator of the Wnt/β-catenin pathway involved in osteoblast differentiation". Cell Death and Differentiation. 22 (6): 912–20. doi: 10.1038/cdd.2014.238 . PMC   4423189 . PMID   25633194.
  10. ↑ Kim HY, Yang DH, Shin SW, Kim MY, Yoon JH, Kim S, et al. (February 2014). "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. doi: 10.1096/fj.13-236216 . PMID   24136587. S2CID   23959096.
  11. 1 2 3 Lee SH, Kim MY, Kim HY, Lee YM, Kim H, Nam KA, et al. (June 2015). "The Dishevelled-binding protein CXXC5 negatively regulates cutaneous wound healing". The Journal of Experimental Medicine. 212 (7): 1061–80. doi: 10.1084/jem.20141601 . PMC   4493411 . PMID   26056233.
  12. 1 2 Kim HY, Choi S, Yoon JH, Lim HJ, Lee H, Choi J, et al. (April 2016). "Small molecule inhibitors of the Dishevelled-CXXC5 interaction are new drug candidates for bone anabolic osteoporosis therapy". EMBO Molecular Medicine. 8 (4): 375–87. doi: 10.15252/emmm.201505714 . PMC   4818757 . PMID   26941261.
  13. 1 2 3 4 Lee SH, Seo SH, Lee DH, Pi LQ, Lee WS, Choi KY (November 2017). "Targeting of CXXC5 by a Competing Peptide Stimulates Hair Regrowth and Wound–Induced Hair Neogenesis". The Journal of Investigative Dermatology. 137 (11): 2260–2269. doi: 10.1016/j.jid.2017.04.038 . PMID   28595998.
  14. ↑ Choi S, Kim HY, Cha PH, Seo SH, Lee C, Choi Y, et al. (April 2019). "CXXC5 mediates growth plate senescence and is a target for enhancement of longitudinal bone growth". Life Science Alliance. 2 (2): e201800254. doi: 10.26508/lsa.201800254 . PMC   6458850 . PMID   30971423.
  15. ↑ Choi S, Kim HY, Cha PH, Seo SH, Lee C, Choi Y, et al. (April 2019). "CXXC5 mediates growth plate senescence and is a target for enhancement of longitudinal bone growth". Life Science Alliance. 2 (2): e201800254. doi: 10.26508/lsa.201800254 . PMC   6458850 . PMID   30971423.

Further reading

This page is based on this Wikipedia article
Text is available under the CC BY-SA 4.0 license; additional terms may apply.
Images, videos and audio are available under their respective licenses.