Caspase 14 Explained

Caspase 14 is an enzyme that in humans is encoded by the CASP14 gene.^{[1] [2] [3]} Orthologs of this gene also exist in other mammals, such as sirenians and cetaceans, though they are inactivated in these two clades. Curiously, manatees, which are sirenians, retain some functional CASP14 genes.^[4]

The CASP14 gene encodes a member of the cysteine-aspartic acid protease (caspase) family. Sequential activation of caspases plays a central role in the execution-phase of cell apoptosis. Caspases exist as inactive proenzymes which undergo proteolytic processing at conserved aspartic residues to produce two subunits, large and small, that dimerize to form the active enzyme. This caspase has been shown to be processed and activated by caspase 8 and caspase 10 in vitro, and by anti-Fas agonist antibody or TNF-related apoptosis inducing ligand in vivo. The expression and processing of this caspase may be involved in keratinocyte terminal differentiation, which is important for the formation of the skin barrier.^[3]

According to the Human Protein Atlas,^[5] the CASP14 protein is enriched in human skin and mainly expressed in the upper layers of the epidermis. The protein is mainly localised to the cytosol according to the Cell Atlas.^[6]

See also

• The Proteolysis Map
• Caspase

Further reading

• Rasmussen HH, van Damme J, Puype M . Microsequences of 145 proteins recorded in the two-dimensional gel protein database of normal human epidermal keratinocytes. . Electrophoresis . 13 . 12 . 960–9 . 1993 . 1286667 . 10.1002/elps.11501301199 . 41855774 . etal.
• Ahmad M, Srinivasula SM, Hegde R . Identification and characterization of murine caspase-14, a new member of the caspase family. . Cancer Res. . 58 . 22 . 5201–5 . 1998 . 9823333 . etal.
• Eckhart L, Ban J, Fischer H, Tschachler E . Caspase-14: analysis of gene structure and mRNA expression during keratinocyte differentiation. . Biochem. Biophys. Res. Commun. . 277 . 3 . 655–9 . 2000 . 11062009 . 10.1006/bbrc.2000.3698 .
• Eckhart L, Declercq W, Ban J . Terminal differentiation of human keratinocytes and stratum corneum formation is associated with caspase-14 activation. . J. Invest. Dermatol. . 115 . 6 . 1148–51 . 2001 . 11121154 . 10.1046/j.1523-1747.2000.00205.x . etal. free .
• Lippens S, Kockx M, Knaapen M . Epidermal differentiation does not involve the pro-apoptotic executioner caspases, but is associated with caspase-14 induction and processing. . Cell Death Differ. . 7 . 12 . 1218–24 . 2001 . 11175259 . 10.1038/sj.cdd.4400785 . etal. free .
• Pistritto G, Jost M, Srinivasula SM . Expression and transcriptional regulation of caspase-14 in simple and complex epithelia. . Cell Death Differ. . 9 . 9 . 995–1006 . 2003 . 12181750 . 10.1038/sj.cdd.4401061 . 23933663 . etal.
• Chien AJ, Presland RB, Kuechle MK . Processing of native caspase-14 occurs at an atypical cleavage site in normal epidermal differentiation. . Biochem. Biophys. Res. Commun. . 296 . 4 . 911–7 . 2002 . 12200134 . 10.1016/S0006-291X(02)02015-6 .
• Rendl M, Ban J, Mrass P . Caspase-14 expression by epidermal keratinocytes is regulated by retinoids in a differentiation-associated manner. . J. Invest. Dermatol. . 119 . 5 . 1150–5 . 2003 . 12445205 . 10.1046/j.1523-1747.2002.19532.x . etal. free .
• Strausberg RL, Feingold EA, Grouse LH . 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 . 2003 . 12477932 . 139241 . 10.1073/pnas.242603899 . 2002PNAS...9916899M . etal. free .
• Lippens S, Kockx M, Denecker G . Vitamin D3 induces caspase-14 expression in psoriatic lesions and enhances caspase-14 processing in organotypic skin cultures. . Am. J. Pathol. . 165 . 3 . 833–41 . 2004 . 15331408 . 1618612 . 10.1016/s0002-9440(10)63346-9. etal.
• Gerhard DS, Wagner L, Feingold EA . The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). . Genome Res. . 14 . 10B . 2121–7 . 2004 . 15489334 . 528928 . 10.1101/gr.2596504 . etal.
• Walsh DS, Borke JL, Singh BB . Psoriasis is characterized by altered epidermal expression of caspase 14, a novel regulator of keratinocyte terminal differentiation and barrier formation. . J. Dermatol. Sci. . 37 . 1 . 61–3 . 2005 . 15619438 . 10.1016/j.jdermsci.2004.10.003 . etal.
• Koenig U, Sommergruber W, Lippens S . Aberrant expression of caspase-14 in epithelial tumors. . Biochem. Biophys. Res. Commun. . 335 . 2 . 309–13 . 2005 . 16061209 . 10.1016/j.bbrc.2005.07.072 .
• Krajewska M, Kim H, Shin E . Tumor-associated alterations in caspase-14 expression in epithelial malignancies. . Clin. Cancer Res. . 11 . 15 . 5462–71 . 2006 . 16061862 . 10.1158/1078-0432.CCR-04-2527 . etal. free .
• Kam DW, Charles AK, Dharmarajan AM . Caspase-14 expression in the human placenta. . Reprod. Biomed. Online . 11 . 2 . 236–43 . 2005 . 16168224 . 10.1016/S1472-6483(10)60964-9 . free .
• Park K, Kuechle MK, Choe Y . Expression and characterization of constitutively active human caspase-14. . Biochem. Biophys. Res. Commun. . 347 . 4 . 941–8 . 2006 . 16854378 . 10.1016/j.bbrc.2006.06.156 . etal.
• White L, Dharmarajan A, Charles A . Caspase-14: a new player in cytotrophoblast differentiation. . Reprod. Biomed. Online . 14 . 3 . 300–7 . 2007 . 17359582 . 10.1016/S1472-6483(10)60871-1 . free .
• Hsu S, Qin H, Dickinson D . Expression of caspase-14 reduces tumorigenicity of skin cancer cells. . In Vivo . 21 . 2 . 279–83 . 2007 . 17436577 . etal.

External links

• The MEROPS online database for peptidases and their inhibitors: C14.018

Notes and References

1. Van de Craen M, Van Loo G, Pype S, Van Criekinge W, Van den brande I, Molemans F, Fiers W, Declercq W, Vandenabeele P . Identification of a new caspase homologue: caspase-14 . Cell Death Differ . 5 . 10 . 838–46 . May 1999 . 10203698 . 10.1038/sj.cdd.4400444 . free .
2. Hu S, Snipas SJ, Vincenz C, Salvesen G, Dixit VM . Caspase-14 is a novel developmentally regulated protease . J Biol Chem . 273 . 45 . 29648–53 . Dec 1998 . 9792675 . 10.1074/jbc.273.45.29648 . free .
3. Web site: Entrez Gene: CASP14 caspase 14, apoptosis-related cysteine peptidase.
4. Steinbinder . Julia . Sachslehner . Attila Placido . Holthaus . Karin Brigit . Eckhart . Leopold . 2024-04-23 . Comparative genomics of sirenians reveals evolution of filaggrin and caspase-14 upon adaptation of the epidermis to aquatic life . Scientific Reports . en . 14 . 1 . 9278 . 10.1038/s41598-024-60099-2 . 2045-2322 . 11039687 . 38653760.
5. Uhlén. Mathias. Fagerberg. Linn. Hallström. Björn M.. Lindskog. Cecilia. Oksvold. Per. Mardinoglu. Adil. Sivertsson. Åsa. Kampf. Caroline. Sjöstedt. Evelina. 2015-01-23. Tissue-based map of the human proteome. Science. en. 347. 6220. 1260419. 10.1126/science.1260419. 0036-8075. 25613900. 802377.
6. Thul. Peter J.. Åkesson. Lovisa. Wiking. Mikaela. Mahdessian. Diana. Geladaki. Aikaterini. Blal. Hammou Ait. Alm. Tove. Asplund. Anna. Björk. Lars. 2017-05-26. A subcellular map of the human proteome. Science. en. 356. 6340. eaal3321. 10.1126/science.aal3321. 0036-8075. 28495876. 10744558.