FASTK explained

Fas-activated serine/threonine kinase is an enzyme that in humans is encoded by the FASTK gene.^{[1] [2] [3]}

The protein encoded by this gene is a member of the serine/threonine protein kinase family. This kinase was shown to be activated rapidly during Fas-mediated apoptosis in Jurkat cells. In response to Fas receptor ligation, it phosphorylates the apoptosis-promoting nuclear RNA-binding protein TIA1. The encoded protein is a strong inducer of lymphocyte apoptosis.

Two transcript variants encoding different isoforms have been found for this gene. The longer one is located in the cell nucleus and cytoplasm, and the shorter one is 34 amino acids at the N-terminus, which is transported to the mitochondrion.^[4]

The mitochondrial FASTK isoform localizes in the mitochondrial granules, where it interacts with the GRSF1 protein and binds to mt-mRNA ND6, the template of the only protein encoded on the light strand of the mitochondrial genome. In the case of FASTK deletion, it was observed loss of ND6 mt-mRNA and a 50-60% decrease in the activity of complex I of the respiratory chain. However, overexpression of this protein resulted in the stabilization of ND6 mt-mRNA ^[5]

Other variants exist, but their full-length natures have not yet been determined.

Further reading

• Auffray C, Behar G, Bois F, Bouchier C, Da Silva C, Devignes MD, Duprat S, Houlgatte R, Jumeau MN, Lamy B . 6 . [IMAGE: molecular integration of the analysis of the human genome and its expression] . Comptes Rendus de l'Académie des Sciences. Série III, Sciences de la Vie . 318 . 2 . 263–272 . February 1995 . 7757816 .
• Maruyama K, Sugano S . Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides . Gene . 138 . 1–2 . 171–174 . January 1994 . 8125298 . 10.1016/0378-1119(94)90802-8 .
• Bonaldo MF, Lennon G, Soares MB . Normalization and subtraction: two approaches to facilitate gene discovery . Genome Research . 6 . 9 . 791–806 . September 1996 . 8889548 . 10.1101/gr.6.9.791 . free .
• Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, Suyama A, Sugano S . Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library . Gene . 200 . 1–2 . 149–156 . October 1997 . 9373149 . 10.1016/S0378-1119(97)00411-3 .
• Li W, Kedersha N, Chen S, Gilks N, Lee G, Anderson P . FAST is a BCL-X(L)-associated mitochondrial protein . Biochemical and Biophysical Research Communications . 318 . 1 . 95–102 . May 2004 . 15110758 . 10.1016/j.bbrc.2004.03.188 .
• 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 . 6 . Towards a proteome-scale map of the human protein-protein interaction network . Nature . 437 . 7062 . 1173–1178 . October 2005 . 16189514 . 10.1038/nature04209 . 4427026 . 2005Natur.437.1173R .
• Oh JH, Yang JO, Hahn Y, Kim MR, Byun SS, Jeon YJ, Kim JM, Song KS, Noh SM, Kim S, Yoo HS, Kim YS, Kim NS . 6 . Transcriptome analysis of human gastric cancer . Mammalian Genome . 16 . 12 . 942–954 . December 2005 . 16341674 . 10.1007/s00335-005-0075-2 . 69278 .
• Izquierdo JM, Valcárcel J . Fas-activated serine/threonine kinase (FAST K) synergizes with TIA-1/TIAR proteins to regulate Fas alternative splicing . The Journal of Biological Chemistry . 282 . 3 . 1539–1543 . January 2007 . 17135269 . 10.1074/jbc.C600198200 . free .
• Simarro M, Mauger D, Rhee K, Pujana MA, Kedersha NL, Yamasaki S, Cusick ME, Vidal M, Garcia-Blanco MA, Anderson P . 6 . Fas-activated serine/threonine phosphoprotein (FAST) is a regulator of alternative splicing . Proceedings of the National Academy of Sciences of the United States of America . 104 . 27 . 11370–11375 . July 2007 . 17592127 . 2040905 . 10.1073/pnas.0704964104 . free . 2007PNAS..10411370S .

Notes and References

1. Tian Q, Taupin J, Elledge S, Robertson M, Anderson P . Fas-activated serine/threonine kinase (FAST) phosphorylates TIA-1 during Fas-mediated apoptosis . The Journal of Experimental Medicine . 182 . 3 . 865–874 . September 1995 . 7544399 . 2192163 . 10.1084/jem.182.3.865 .
2. Li W, Simarro M, Kedersha N, Anderson P . FAST is a survival protein that senses mitochondrial stress and modulates TIA-1-regulated changes in protein expression . Molecular and Cellular Biology . 24 . 24 . 10718–10732 . December 2004 . 15572676 . 533970 . 10.1128/MCB.24.24.10718-10732.2004 .
3. Web site: Entrez Gene: FASTK Fas-activated serine/threonine kinase.
4. Jourdain AA, Popow J, de la Fuente MA, Martinou JC, Anderson P, Simarro M . The FASTK family of proteins: emerging regulators of mitochondrial RNA biology . Nucleic Acids Research . 45 . 19 . 10941–10947 . November 2017 . 29036396 . 5737537 . 10.1093/nar/gkx772 .
5. Jourdain AA, Koppen M, Rodley CD, Maundrell K, Gueguen N, Reynier P, Guaras AM, Enriquez JA, Anderson P, Simarro M, Martinou JC . 6 . A mitochondria-specific isoform of FASTK is present in mitochondrial RNA granules and regulates gene expression and function . Cell Reports . 10 . 7 . 1110–1121 . February 2015 . 25704814 . 10.1016/j.celrep.2015.01.063 . free . 10261/157664 . free .