T-cell lymphoma invasion and metastasis-inducing protein 1 explained

Rho guanine nucleotide exchange factor TIAM1 is a protein that in humans is encoded by the TIAM1 gene.^{[1] [2] [3]}

Structure

TIAM1 is tightly associate with BAIAP2 as a subunit. It contains one DH (DBL-homology) domain, one PDZ domain, two PH domains and one Ras-binding RBD domain.

Function

TIAM1 modulates the activity of Rho GTP-binding proteins and connects extracellular signals to cytoskeletal activities. In addition, TIAM1 activates Rac1, CDC42, and to a lesser extent RhoA.

Clinical significance

TIAM1 is found in virtually all tumor cell lines examined including B- and T-lymphomas, neuroblastomas, melanomas and carcinomas.

Interactions

T-cell lymphoma invasion and metastasis-inducing protein 1 has been shown to interact with ANK1,^[4] Myc,^[5] RAC1^{[6] [7]} and PPP1R9B.^[8]

Tiam1 interacts also with para-cingulin, that plays a role in recruiting Tiam1 to junctions and thus activate Rac1 at epithelial junctions.^[9]

Further reading

• Habets GG, van der Kammen RA, Stam JC, Michiels F, Collard JG . Sequence of the human invasion-inducing TIAM1 gene, its conservation in evolution and its expression in tumor cell lines of different tissue origin . Oncogene . 10 . 7 . 1371–1376 . Apr 1995 . 7731688 .
• Habets GG, van der Kammen RA, Jenkins NA, Gilbert DJ, Copeland NG, Hagemeijer A, Collard JG . The invasion-inducing TIAM1 gene maps to human chromosome band 21q22 and mouse chromosome 16 . Cytogenetics and Cell Genetics . 70 . 1–2 . 48–51 . 1995 . 7736788 . 10.1159/000133989 . 46831770 .
• Michiels F, Habets GG, Stam JC, van der Kammen RA, Collard JG . A role for Rac in Tiam1-induced membrane ruffling and invasion . Nature . 375 . 6529 . 338–340 . May 1995 . 7753201 . 10.1038/375338a0 . 1995Natur.375..338M . 4251212 .
• Andersson B, Wentland MA, Ricafrente JY, Liu W, Gibbs RA . A "double adaptor" method for improved shotgun library construction . Analytical Biochemistry . 236 . 1 . 107–113 . Apr 1996 . 8619474 . 10.1006/abio.1996.0138 .
• Michiels F, Stam JC, Hordijk PL, van der Kammen RA, Ruuls-Van Stalle L, Feltkamp CA, Collard JG . Regulated membrane localization of Tiam1, mediated by the NH2-terminal pleckstrin homology domain, is required for Rac-dependent membrane ruffling and C-Jun NH2-terminal kinase activation . The Journal of Cell Biology . 137 . 2 . 387–398 . Apr 1997 . 9128250 . 2139766 . 10.1083/jcb.137.2.387 .
• Fleming IN, Elliott CM, Buchanan FG, Downes CP, Exton JH . Ca2+/calmodulin-dependent protein kinase II regulates Tiam1 by reversible protein phosphorylation . The Journal of Biological Chemistry . 274 . 18 . 12753–12758 . Apr 1999 . 10212259 . 10.1074/jbc.274.18.12753 . free .
• Bourguignon LY, Zhu H, Shao L, Chen YW . CD44 interaction with tiam1 promotes Rac1 signaling and hyaluronic acid-mediated breast tumor cell migration . The Journal of Biological Chemistry . 275 . 3 . 1829–1838 . Jan 2000 . 10636882 . 10.1074/jbc.275.3.1829 . free .
• Crompton AM, Foley LH, Wood A, Roscoe W, Stokoe D, McCormick F, Symons M, Bollag G . Regulation of Tiam1 nucleotide exchange activity by pleckstrin domain binding ligands . The Journal of Biological Chemistry . 275 . 33 . 25751–25759 . Aug 2000 . 10835422 . 10.1074/jbc.M002050200 . free .
• Bourguignon LY, Zhu H, Shao L, Chen YW . Ankyrin-Tiam1 interaction promotes Rac1 signaling and metastatic breast tumor cell invasion and migration . The Journal of Cell Biology . 150 . 1 . 177–191 . Jul 2000 . 10893266 . 2185563 . 10.1083/jcb.150.1.177 .
• Worthylake DK, Rossman KL, Sondek J . Crystal structure of Rac1 in complex with the guanine nucleotide exchange region of Tiam1 . Nature . 408 . 6813 . 682–688 . Dec 2000 . 11130063 . 10.1038/35047014 . 2000Natur.408..682W . 4429919 .
• Otsuki Y, Tanaka M, Yoshii S, Kawazoe N, Nakaya K, Sugimura H . Tumor metastasis suppressor nm23H1 regulates Rac1 GTPase by interaction with Tiam1 . Proceedings of the National Academy of Sciences of the United States of America . 98 . 8 . 4385–4390 . Apr 2001 . 11274357 . 31844 . 10.1073/pnas.071411598 . 2001PNAS...98.4385O . free .
• Gao Y, Xing J, Streuli M, Leto TL, Zheng Y . Trp(56) of rac1 specifies interaction with a subset of guanine nucleotide exchange factors . The Journal of Biological Chemistry . 276 . 50 . 47530–47541 . Dec 2001 . 11595749 . 10.1074/jbc.M108865200 . free .
• Buchsbaum RJ, Connolly BA, Feig LA . Interaction of Rac exchange factors Tiam1 and Ras-GRF1 with a scaffold for the p38 mitogen-activated protein kinase cascade . Molecular and Cellular Biology . 22 . 12 . 4073–4085 . Jun 2002 . 12024021 . 133864 . 10.1128/MCB.22.12.4073-4085.2002 .
• Lambert JM, Lambert QT, Reuther GW, Malliri A, Siderovski DP, Sondek J, Collard JG, Der CJ . Tiam1 mediates Ras activation of Rac by a PI(3)K-independent mechanism . Nature Cell Biology . 4 . 8 . 621–625 . Aug 2002 . 12134164 . 10.1038/ncb833 . 21639425 .
• Wennerberg K, Ellerbroek SM, Liu RY, Karnoub AE, Burridge K, Der CJ . RhoG signals in parallel with Rac1 and Cdc42 . The Journal of Biological Chemistry . 277 . 49 . 47810–47817 . Dec 2002 . 12376551 . 10.1074/jbc.M203816200 . free .
• Otsuki Y, Tanaka M, Kamo T, Kitanaka C, Kuchino Y, Sugimura H . Guanine nucleotide exchange factor, Tiam1, directly binds to c-Myc and interferes with c-Myc-mediated apoptosis in rat-1 fibroblasts . The Journal of Biological Chemistry . 278 . 7 . 5132–5140 . Feb 2003 . 12446731 . 10.1074/jbc.M206733200 . free .
• Buchsbaum RJ, Connolly BA, Feig LA . Regulation of p70 S6 kinase by complex formation between the Rac guanine nucleotide exchange factor (Rac-GEF) Tiam1 and the scaffold spinophilin . The Journal of Biological Chemistry . 278 . 21 . 18833–18841 . May 2003 . 12531897 . 10.1074/jbc.M207876200 . free .

Notes and References

1. Web site: Entrez Gene: TIAM1 T-cell lymphoma invasion and metastasis 1.
2. Chen H, Antonarakis SE . Localization of a human homolog of the mouse Tiam-1 gene to chromosome 21q22.1 . Genomics . 30 . 1 . 123–127 . Nov 1995 . 8595894 . 10.1006/geno.1995.0025 .
3. Uhlenbrock K, Eberth A, Herbrand U, Daryab N, Stege P, Meier F, Friedl P, Collard JG, Ahmadian MR . The RacGEF Tiam1 inhibits migration and invasion of metastatic melanoma via a novel adhesive mechanism . Journal of Cell Science . 117 . Pt 20 . 4863–4871 . Sep 2004 . 15340013 . 10.1242/jcs.01367 . free .
4. Bourguignon LY, Zhu H, Shao L, Chen YW . Ankyrin-Tiam1 interaction promotes Rac1 signaling and metastatic breast tumor cell invasion and migration . The Journal of Cell Biology . 150 . 1 . 177–191 . Jul 2000 . 10893266 . 2185563 . 10.1083/jcb.150.1.177 .
5. Otsuki Y, Tanaka M, Kamo T, Kitanaka C, Kuchino Y, Sugimura H . Guanine nucleotide exchange factor, Tiam1, directly binds to c-Myc and interferes with c-Myc-mediated apoptosis in rat-1 fibroblasts . The Journal of Biological Chemistry . 278 . 7 . 5132–5140 . Feb 2003 . 12446731 . 10.1074/jbc.M206733200 . free .
6. Worthylake DK, Rossman KL, Sondek J . Crystal structure of Rac1 in complex with the guanine nucleotide exchange region of Tiam1 . Nature . 408 . 6813 . 682–688 . Dec 2000 . 11130063 . 10.1038/35047014 . 2000Natur.408..682W . 4429919 .
7. Gao Y, Xing J, Streuli M, Leto TL, Zheng Y . Trp(56) of rac1 specifies interaction with a subset of guanine nucleotide exchange factors . The Journal of Biological Chemistry . 276 . 50 . 47530–47541 . Dec 2001 . 11595749 . 10.1074/jbc.M108865200 . free .
8. Buchsbaum RJ, Connolly BA, Feig LA . Regulation of p70 S6 kinase by complex formation between the Rac guanine nucleotide exchange factor (Rac-GEF) Tiam1 and the scaffold spinophilin . The Journal of Biological Chemistry . 278 . 21 . 18833–18841 . May 2003 . 12531897 . 10.1074/jbc.M207876200 . free .
9. Guillemot L, Paschoud S, Jond L, Foglia A, Citi S . Paracingulin regulates the activity of Rac1 and RhoA GTPases by recruiting Tiam1 and GEF-H1 to epithelial junctions . Molecular Biology of the Cell . 19 . 10 . 4442–4453 . Oct 2008 . 18653465 . 2555940 . 10.1091/mbc.E08-06-0558 .