Caspase 12 Explained

Caspase 12 is a protein that in humans is encoded by the CASP12 gene. The protein belongs to a family of enzymes called caspases which cleave their substrates at C-terminal aspartic acid residues. It is closely related to caspase 1 and other members of the caspase family, known as inflammatory caspases, which process and activate inflammatory cytokines such as interleukin 1 and interleukin 18.

Gene

It is found on chromosome 11 in humans in a locus with other inflammatory caspases.[1] CASP12 orthologs[2] have been identified in numerous mammals for which complete genome data are available.

Clinical significance

The CASP12 gene is subject to polymorphism, which can generate a full-length caspase protein (Csp12L) or an inactive truncated form (Csp12S). The functional form appears to be confined to people of African descent and is linked with susceptibility to sepsis; people carrying the functional gene have decreased responses to bacterial molecules such as lipopolysaccharide (LPS).[3] [4]

A study in May 2009 by McGill University Health Centre has suggested that estrogen may serve to block the production of caspase-12, resulting in a stronger inflammatory reaction to bacterial pathogens. The trials were carried out on laboratory mice which had been implanted with the human caspase-12 gene.[5] [6] [7]

The inactive truncated form (Csp12S) of the CASP12 gene was spread and nearly fixed in non-African populations due to positive selection beginning perhaps 60–100 thousand years ago. Its selective advantage is thought to be sepsis resistance in populations that experienced more infectious diseases as population sizes and densities increased.[8] [9]

External links

Notes and References

  1. Fischer H, Koenig U, Eckhart L, Tschachler E . Human caspase 12 has acquired deleterious mutations . Biochem. Biophys. Res. Commun. . 293 . 2 . 722–6 . 2002 . 12054529 . 10.1016/S0006-291X(02)00289-9.
  2. Web site: OrthoMaM phylogenetic marker: CASP12 coding sequence .
  3. Saleh M, Vaillancourt JP, Graham RK, Huyck M, Srinivasula SM, Alnemri ES, Steinberg MH, Nolan V, Baldwin CT, Hotchkiss RS, Buchman TG, Zehnbauer BA, Hayden MR, Farrer LA, Roy S, Nicholson DW . Differential modulation of endotoxin responsiveness by human caspase-12 polymorphisms . Nature . 429 . 6987 . 75–9 . 2004 . 15129283 . 10.1038/nature02451. 2004Natur.429...75S . free .
  4. Saleh, Maya Mathison . John C. Wolinski . Melissa K. Bensinger . Steve J. Fitzgerald . Patrick Droin . Nathalie Ulevitch . Richard J. Green . Douglas R. Nicholson . Donald W. . Enhanced bacterial clearance and sepsis resistance in caspase-12-deficient mice . Nature . 440 . 7087 . 1064–1068 . 2006 . 10.1038/nature04656 . 16625199 . 2006Natur.440.1064S . 4321520 .
  5. Yeretssian G, Doiron K, Shao W, Leavitt BR, Hayden MR, Nicholson DW, Saleh M . Gender differences in expression of the human caspase-12 long variant determines susceptibility to Listeria monocytogenes infection . Proc. Natl. Acad. Sci. U.S.A. . 106. 22. 9016–20. May 2009 . 19447924 . 10.1073/pnas.0813362106 . 2690057 . 2009PNAS..106.9016Y . free .
  6. Web site: Man flu: real or myth? . 2009-05-18 . Health . NHS UK . 23 May 2009 . 16 February 2010 . https://web.archive.org/web/20100216113214/http://www.nhs.uk/news/2009/05May/Pages/Manflurealormyth.aspx . dead .
  7. Web site: Women 'fight off disease better' . 2009-05-13 . Health . BBC News . 2009-05-13.
  8. 10.1086/503116 . 78 . 4 . Spread of an Inactive Form of Caspase-12 in Humans Is Due to Recent Positive Selection . The American Journal of Human Genetics . 659–670 . 16532395 . 1424700. 2006 . Xue . Yali . Daly . Allan . Yngvadottir . Bryndis . Liu . Mengning . Coop . Graham . Kim . Yuseob . Sabeti . Pardis . Pardis Sabeti . Chen . Yuan . Stalker . Jim . Huckle . Elizabeth . Burton . John . Leonard . Steven . Rogers . Jane . Tyler-Smith . Chris .
  9. 10.1371/journal.pbio.0040052 . 4 . 3 . Gene Losses during Human Origins . PLOS Biology . e52 . 16464126 . 1361800. 2006 . Wang . Xiaoxia . Grus . Wendy E. . Zhang . Jianzhi . free .

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