DUSP1 explained

Dual specificity protein phosphatase 1 is an enzyme that in humans is encoded by the DUSP1 gene.^{[1] [2]}

Function

The expression of DUSP1 gene is induced in human skin fibroblasts by oxidative/heat stress and growth factors. It specifies a protein with structural features similar to members of the non-receptor-type protein-tyrosine phosphatase family, and which has significant amino-acid sequence similarity to a Tyr/Ser-protein phosphatase encoded by the late gene H1 of vaccinia virus. The bacterially expressed and purified DUSP1 protein has intrinsic phosphatase activity, and specifically inactivates mitogen-activated protein (MAP) kinase in vitro by the concomitant dephosphorylation of both its phosphothreonine and phosphotyrosine residues. Furthermore, it suppresses the activation of MAP kinase by oncogenic ras in extracts of Xenopus oocytes. Thus, DUSP1 may play an important role in the human cellular response to environmental stress as well as in the negative regulation of cellular proliferation.^[3]

Interactions

DUSP1 has been shown to interact with MAPK14,^{[4] [5]} MAPK1^{[5] [6]} and MAPK8.^[5]

Further reading

• Martell KJ, Angelotti T, Ullrich A . The "VH1-like" dual-specificity protein tyrosine phosphatases . Molecules and Cells . 8 . 1 . 2–11 . Feb 1998 . 10.1016/S1016-8478(23)13385-1 . 9571625 . free .
• Keyse SM . Protein phosphatases and the regulation of MAP kinase activity . Seminars in Cell & Developmental Biology . 9 . 2 . 143–52 . Apr 1998 . 9599409 . 10.1006/scdb.1997.0219 .
• Abraham SM, Clark AR . Dual-specificity phosphatase 1: a critical regulator of innate immune responses . Biochemical Society Transactions . 34 . Pt 6 . 1018–23 . Dec 2006 . 17073741 . 10.1042/BST0341018 .
• Raingeaud J, Gupta S, Rogers JS, Dickens M, Han J, Ulevitch RJ, Davis RJ . Pro-inflammatory cytokines and environmental stress cause p38 mitogen-activated protein kinase activation by dual phosphorylation on tyrosine and threonine . The Journal of Biological Chemistry . 270 . 13 . 7420–6 . Mar 1995 . 7535770 . 10.1074/jbc.270.13.7420 . free .
• Kwak SP, Hakes DJ, Martell KJ, Dixon JE . Isolation and characterization of a human dual specificity protein-tyrosine phosphatase gene . The Journal of Biological Chemistry . 269 . 5 . 3596–604 . Feb 1994 . 10.1016/S0021-9258(17)41905-3 . 8106404 . free .
• Emslie EA, Jones TA, Sheer D, Keyse SM . The CL100 gene, which encodes a dual specificity (Tyr/Thr) MAP kinase phosphatase, is highly conserved and maps to human chromosome 5q34 . Human Genetics . 93 . 5 . 513–6 . May 1994 . 8168826 . 10.1007/BF00202814 . 12590731 .
• Sun H, Charles CH, Lau LF, Tonks NK . MKP-1 (3CH134), an immediate early gene product, is a dual specificity phosphatase that dephosphorylates MAP kinase in vivo . Cell . 75 . 3 . 487–93 . Nov 1993 . 8221888 . 10.1016/0092-8674(93)90383-2 . 29988777 .
• Charles CH, Sun H, Lau LF, Tonks NK . The growth factor-inducible immediate-early gene 3CH134 encodes a protein-tyrosine-phosphatase . Proceedings of the National Academy of Sciences of the United States of America . 90 . 11 . 5292–6 . Jun 1993 . 8389479 . 46702 . 10.1073/pnas.90.11.5292 . 1993PNAS...90.5292C . free .
• Alessi DR, Smythe C, Keyse SM . The human CL100 gene encodes a Tyr/Thr-protein phosphatase which potently and specifically inactivates MAP kinase and suppresses its activation by oncogenic ras in Xenopus oocyte extracts . Oncogene . 8 . 7 . 2015–20 . Jul 1993 . 8390041 .
• Brondello JM, Pouysségur J, McKenzie FR . Reduced MAP kinase phosphatase-1 degradation after p42/p44MAPK-dependent phosphorylation . Science . 286 . 5449 . 2514–7 . Dec 1999 . 10617468 . 10.1126/science.286.5449.2514 .
• Hutter D, Chen P, Barnes J, Liu Y . Catalytic activation of mitogen-activated protein (MAP) kinase phosphatase-1 by binding to p38 MAP kinase: critical role of the p38 C-terminal domain in its negative regulation . The Biochemical Journal . 352 . 1. 155–63 . Nov 2000 . 11062068 . 1221442 . 10.1042/0264-6021:3520155 .
• Slack DN, Seternes OM, Gabrielsen M, Keyse SM . Distinct binding determinants for ERK2/p38alpha and JNK map kinases mediate catalytic activation and substrate selectivity of map kinase phosphatase-1 . The Journal of Biological Chemistry . 276 . 19 . 16491–500 . May 2001 . 11278799 . 10.1074/jbc.M010966200 . free .
• Manzano RG, Montuenga LM, Dayton M, Dent P, Kinoshita I, Vicent S, Gardner GJ, Nguyen P, Choi YH, Trepel J, Auersperg N, Birrer MJ . CL100 expression is down-regulated in advanced epithelial ovarian cancer and its re-expression decreases its malignant potential . Oncogene . 21 . 28 . 4435–47 . Jun 2002 . 12080474 . 10.1038/sj.onc.1205542 . free . 10171/20183 . free .
• Imasato A, Desbois-Mouthon C, Han J, Kai H, Cato AC, Akira S, Li JD . Inhibition of p38 MAPK by glucocorticoids via induction of MAPK phosphatase-1 enhances nontypeable Haemophilus influenzae-induced expression of toll-like receptor 2 . The Journal of Biological Chemistry . 277 . 49 . 47444–50 . Dec 2002 . 12356755 . 10.1074/jbc.M208140200 . free .
• Lasa M, Abraham SM, Boucheron C, Saklatvala J, Clark AR . Dexamethasone causes sustained expression of mitogen-activated protein kinase (MAPK) phosphatase 1 and phosphatase-mediated inhibition of MAPK p38 . Molecular and Cellular Biology . 22 . 22 . 7802–11 . Nov 2002 . 12391149 . 134716 . 10.1128/MCB.22.22.7802-7811.2002 .
• Denkert C, Schmitt WD, Berger S, Reles A, Pest S, Siegert A, Lichtenegger W, Dietel M, Hauptmann S . Expression of mitogen-activated protein kinase phosphatase-1 (MKP-1) in primary human ovarian carcinoma . International Journal of Cancer . 102 . 5 . 507–13 . Dec 2002 . 12432554 . 10.1002/ijc.10746 . 45750943 . free .

Notes and References

1. Keyse SM, Emslie EA . Oxidative stress and heat shock induce a human gene encoding a protein-tyrosine phosphatase . Nature . 359 . 6396 . 644–7 . Oct 1992 . 1406996 . 10.1038/359644a0 . 1992Natur.359..644K . 4307895 .
2. Martell KJ, Kwak S, Hakes DJ, Dixon JE, Trent JM . Chromosomal localization of four human VH1-like protein-tyrosine phosphatases . Genomics . 22 . 2 . 462–4 . Jul 1994 . 7806236 . 10.1006/geno.1994.1411 . 2027.42/31442 . free .
3. Web site: Entrez Gene: DUSP1 dual specificity phosphatase 1.
4. Tanoue T, Yamamoto T, Maeda R, Nishida E . A Novel MAPK phosphatase MKP-7 acts preferentially on JNK/SAPK and p38 alpha and beta MAPKs . The Journal of Biological Chemistry . 276 . 28 . 26629–39 . Jul 2001 . 11359773 . 10.1074/jbc.M101981200 . free .
5. Slack DN, Seternes OM, Gabrielsen M, Keyse SM . Distinct binding determinants for ERK2/p38alpha and JNK map kinases mediate catalytic activation and substrate selectivity of map kinase phosphatase-1 . The Journal of Biological Chemistry . 276 . 19 . 16491–500 . May 2001 . 11278799 . 10.1074/jbc.M010966200 . free .
6. Calvisi DF, Pinna F, Meloni F, Ladu S, Pellegrino R, Sini M, Daino L, Simile MM, De Miglio MR, Virdis P, Frau M, Tomasi ML, Seddaiu MA, Muroni MR, Feo F, Pascale RM . Dual-specificity phosphatase 1 ubiquitination in extracellular signal-regulated kinase-mediated control of growth in human hepatocellular carcinoma . Cancer Research . 68 . 11 . 4192–200 . Jun 2008 . 18519678 . 10.1158/0008-5472.CAN-07-6157 . free .