TASP1 explained

Threonine aspartase 1 is an enzyme that in humans is encoded by the TASP1 gene.^{[1] [2]}

Function

This gene encodes an endopeptidase that cleaves specific substrates following aspartate residues. The encoded protein undergoes posttranslational autoproteolytic processing to generate alpha and beta subunits, which reassemble into the active alpha2-beta2 heterotetramer. It is required to cleave MLL, a protein required for the maintenance of HOX gene expression, and TFIIA, a basal transcription factor. Cleavage of TFIIA has been found to drive spermatogenesis.^[3]

Alternatively spliced transcript variants have been described, but their biological validity has not been determined.

Clinical significance

Taspase1 is overexpressed in primary human cancers and functions as a non-oncogene addiction protease that coordinates cancer cell proliferation and apoptosis. Therefore, Taspase1 may serve as a novel anti-cancer therapeutic target.^[4]

Further reading

• Zhou H . Uncleaved TFIIA is a substrate for taspase 1 and active in transcription . Mol. Cell. Biol. . 26 . 7 . 2728–35 . 2006 . 16537915 . 10.1128/MCB.26.7.2728-2735.2006 . 1430320 . vanc. Spicuglia S . Hsieh JJ . 3 . Mitsiou . D. J. . Hoiby . T. . Veenstra . G. J. C. . Korsmeyer . S. J. . Stunnenberg . H. G. .
• Khan JA, Dunn BM, Tong L . Crystal structure of human Taspase1, a crucial protease regulating the function of MLL . Structure . 13 . 10 . 1443–52 . 2006 . 16216576 . 10.1016/j.str.2005.07.006 . free .
• Gerhard DS . 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 . 10.1101/gr.2596504 . 528928 . vanc. Wagner L . Feingold EA . 3 . Shenmen . CM . Grouse . LH . Schuler . G . Klein . SL . Old . S . Rasooly . R .
• Ota T . Complete sequencing and characterization of 21,243 full-length human cDNAs . Nat. Genet. . 36 . 1 . 40–5 . 2004 . 14702039 . 10.1038/ng1285 . vanc. Suzuki Y . Nishikawa T . 3 . Otsuki . Tetsuji . Sugiyama . Tomoyasu . Irie . Ryotaro . Wakamatsu . Ai . Hayashi . Koji . Sato . Hiroyuki . free .
• Hsieh JJ . Proteolytic cleavage of MLL generates a complex of N- and C-terminal fragments that confers protein stability and subnuclear localization . Mol. Cell. Biol. . 23 . 1 . 186–94 . 2003 . 12482972 . 10.1128/MCB.23.1.186-194.2003 . 140678 . vanc. Ernst P . Erdjument-Bromage H . 3 . Tempst . P. . Korsmeyer . S. J. .
• Strausberg RL . 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 . 10.1073/pnas.242603899 . 139241 . vanc. Feingold EA . Grouse LH . 3 . Derge . JG . Klausner . RD . Collins . FS . Wagner . L . Shenmen . CM . Schuler . GD . 2002PNAS...9916899M . free .
• Deloukas P . The DNA sequence and comparative analysis of human chromosome 20 . Nature . 414 . 6866 . 865–71 . 2002 . 11780052 . 10.1038/414865a . vanc. Matthews LH . Ashurst J . 3 . Burton . J. . Gilbert . J. G. R. . Jones . M. . Stavrides . G. . Almeida . J. P. . Babbage . A. K. . 2001Natur.414..865D . free .

Notes and References

1. Hsieh JJ, Cheng EH, Korsmeyer SJ . Taspase1: a threonine aspartase required for cleavage of MLL and proper HOX gene expression . Cell . 115 . 3 . 293–303 . Nov 2003 . 14636557 . 10.1016/S0092-8674(03)00816-X . 18952302 . free .
2. Web site: Entrez Gene: TASP1 taspase, threonine aspartase, 1.
3. 24176642. 3947863. 2013. Oyama. T. Cleavage of TFIIA by Taspase1 activates TRF2-specified mammalian male germ cell programs. Developmental Cell. 27. 2. 188–200. Sasagawa. S. Takeda. S. Hess. R. A.. Lieberman. P. M.. Cheng. E. H.. Hsieh. J. J.. 10.1016/j.devcel.2013.09.025.
4. Chen DY, Liu H, Takeda S, Tu HC, Sasagawa S, Van Tine BA, Lu D, Cheng EH, Hsieh JJ . Taspase1 functions as a non-oncogene addiction protease that coordinates cancer cell proliferation and apoptosis . Cancer Res. . 70 . 13 . 5358–67 . July 2010 . 20516119 . 2909739 . 10.1158/0008-5472.CAN-10-0027 .