Abstract
The 14-3-3 proteins are a part of an emerging family of proteins and protein domains that bind to serine/threonine-phosphorylated residues in a context specific manner, analogous to the Src homology 2 (SH2) and phospho-tyrosine binding (PTB) domains. 14-3-3 proteins bind and regulate key proteins involved in various physiological processes such as intracellular signaling (e.g. Raf, MLK, MEKK, PI-3 kinase, IRS-1), cell cycling (e.g. Cdc25, Wee1, CDK2, centrosome), apoptosis (e.g. BAD, ASK-1) and transcription regulation (e.g. FKHRL1, DAF-16, p53, TAZ, TLX-2, histone deacetylase). In contrast to SH2 and PTB domains, which serve mainly to mediate protein-protein interactions, 14-3-3 proteins in many cases alter the function of the target protein, thus allowing them to serve as direct regulators of their targets. This review focuses on the various mechanisms employed by the 14-3-3 proteins in the regulation of their diverse targets, the structural basis for 14-3-3-target protein interaction with emphasis on the role of 14-3-3 dimerization in target protein binding and regulation and provides an insight on 14-3-3 regulation itself.
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References
Aitken A, Howell S, Jones D, Madrazo J, Martin H, Patel Y, Robinson K . 1995a Mol. Cell. Biochem. 149–150: 41–49
Aitken A, Howell S, Jones D, Madrazo J, Patel Y . 1995b J. Biol. Chem. 270: 5706–5709
Aitken A, Jones D, Soneji Y, Howell S . 1995c Biochem. Soc. Trans. 23: 605–611
Barinaga M . 1999 Science 283: 1247–1249
Benzing T, Yaffe MB, Arnould T, Sellin L, Schermer B, Schilling B, Schreiber R, Kunzelmann K, Leparc GG, Kim E, Walz G . 2000 J. Biol. Chem. 275: 28167–28172
Bihn EA, Paul AL, Wang SW, Erdos GW, Ferl RJ . 1997 Plant J. 12: 1439–1445
Bonnefoy-Berard N, Liu YC, von Willebrand M, Sung A, Elly C, Mustelin T, Yoshida H, Ishizaka K, Altman A . 1995 Proc. Natl. Acad. Sci. USA 92: 10142–10146
Braselmann S, McCormick F . 1995 EMBO J. 14: 4839–4848
Broadie K, Rushton E, Skoulakis EM, Davis RL . 1997 Neuron 19: 391–402
Brunet A, Bonni A, Zigmond MJ, Lin MZ, Juo P, Hu LS, Anderson MJ, Arden KC, Blenis J, Greenberg ME . 1999 Cell 96: 857–868
Cahill CM, Tzivion G, Nasrin N, Ogg S, Dore J, Ruvkun G, Alexander-Bridges M . 2001 J. Biol. Chem. 276: 13402–13410
Chan TA, Hermeking H, Lengauer C, Kinzler KW, Vogelstein B . 1999 Nature 401: 616–620
Chang HC, Rubin GM . 1997 Genes Dev. 11: 1132–1139
Chapman T, McKeel Jr DW, Morris JC . 2000 Neurology 55: 1396–1397
Chen F, Wagner PD . 1994 FEBS Lett. 347: 128–132
Chiang CW, Harris G, Ellig C, Masters SC, Subramanian R, Shenolikar S, Wadzinski BE, Yang E . 2001 Blood 97: 1289–1297
Chung HJ, Sehnke PC, Ferl RJ . 1999 Trends Plant Sci. 4: 367–371
Conklin DS, Galaktionov K, Beach D . 1995 Proc. Natl. Acad. Sci. USA 92: 7892–7896
Cotelle V, Meek SE, Provan F, Milne FC, Morrice N, MacKintosh C . 2000 EMBO J. 19: 2869–2876
Craparo A, Freund R, Gustafson TA . 1997 J. Biol. Chem. 272: 11663–11669
Dalal SN, Schweitzer CM, Gan J, DeCaprio JA . 1999 Mol. Cell. Biol. 19: 4465–4479
Datta SR, Katsov A, Hu L, Petros A, Fesik SW, Yaffe MB, Greenberg ME . 2000 Mol. Cell. 6: 41–51
Dent P, Jelinek T, Morrison DK, Weber MJ, Sturgill TW . 1995 Science 268: 1902–1906
Dubois T, Howell S, Amess B, Kerai P, Learmonth M, Madrazo J, Chaudhri M, Rittinger K, Scarabel M, Soneji Y, Aitken A . 1997a J. Protein Chem. 16: 513–522
Dubois T, Rommel C, Howell S, Steinhussen U, Soneji Y, Morrice N, Moelling K, Aitken A . 1997b J. Biol. Chem. 272: 28882–28888
Fanger GR, Widmann C, Porter AC, Sather S, Johnson GL, Vaillancourt RR . 1998 J. Biol. Chem. 273: 3476–3483
Fantl WJ, Muslin AJ, Kikuchi A, Martin JA, MacNicol AM, Gross RW, Williams LT . 1994 Nature 371: 612–614
Ferguson AT, Evron E, Umbricht CB, Pandita TK, Chan TA, Hermeking H, Marks JR, Lambers AR, Futreal PA, Stampfer MR, Sukumar S . 2000 Proc. Natl. Acad. Sci. USA 97: 6049–6054
Finnie C, Borch J, Collinge DB . 1999 Plant Mol. Biol. 40: 545–554
Ford JC, al-Khodairy F, Fotou E, Sheldrick KS, Griffiths DJ, Carr AM . 1994 Science 265: 533–535
Freed E, Symons M, Macdonald SG, McCormick F, Ruggieri R . 1994 Science 265: 1713–1716
Fu H, Subramanian RR, Masters SC . 2000 Annu. Rev. Pharmacol. Toxicol. 40: 617–647
Fu H, Xia K, Pallas DC, Cui C, Conroy K, Narsimhan RP, Mamon H, Collier RJ, Roberts TM . 1994 Science 266: 126–129
Furlanetto RW, Dey BR, Lopaczynski W, Nissley SP . 1997 Biochem. J. 327: 765–771
Furukawa Y, Ikuta N, Omata S, Yamauchi T, Isobe T, Ichimura T . 1993 Biochem. Biophys. Res. Commun. 194: 144–149
Garcia-Guzman M, Dolfi F, Russello M, Vuori K . 1999 J. Biol. Chem. 274: 5762–5768
Green AJ, Knight RS, Macleod MA, Lowman A, Will RG . 2001 Neurology 56: 986–987
Grozinger CM, Schreiber SL . 2000 Proc. Natl. Acad. Sci. USA 97: 7835–7840
Gu M, Du X . 1998 J. Biol. Chem. 273: 33465–33471
Hashiguchi M, Sobue K, Paudel HK . 2000 J. Biol. Chem. 275: 25247–25254
Hermeking H, Lengauer C, Polyak K, He TC, Zhang L, Thiagalingam S, Kinzler KW, Vogelstein B . 1997 Mol. Cell. 1: 3–11
Honda R, Ohba Y, Yasuda H . 1997 Biochem. Biophys. Res. Commun. 230: 262–265
Hsu SY, Kaipia A, Zhu L, Hsueh AJ . 1997 Mol. Endocrinol. 11: 1858–1867
Hunter T . 2000 Cell 100: 113–127
Ichimura T, Isobe T, Okuyama T, Takahashi N, Araki K, Kuwano R, Takahashi Y . 1988 Proc. Natl. Acad. Sci. USA 85: 7084–7088
Ichimura T, Ito M, Itagaki C, Takahashi M, Horigome T, Omata S, Ohno S, Isobe T . 1997 FEBS Lett. 413: 273–276
Ichimura T, Uchiyama J, Kunihiro O, Ito M, Horigome T, Omata S, Shinkai F, Kaji H, Isobe T . 1995 J. Biol. Chem. 270: 28515–28518
Irie K, Gotoh Y, Yashar BM, Errede B, Nishida E, Matsumoto K . 1994 Science 265: 1716–1719
Jelinek T, Dent P, Sturgill TW, Weber MJ . 1996 Mol. Cell. Biol. 16: 1027–1034
Jones DH, Ley S, Aitken A . 1995 FEBS Lett. 368: 55–58
Kanai F, Marignani PA, Sarbassova D, Yagi R, Hall RA, Donowitz M, Hisaminato A, Fujiwara T, Ito Y, Cantley LC, Yaffe MB . 2000 EMBO J. 19: 6778–6791
Kay BK, Williamson MP, Sudol M . 2000 FASEB J. 14: 231–241
Kockel L, Vorbruggen G, Jackle H, Mlodzik M, Bohmann D . 1997 Genes Dev. 11: 1140–1147
Kosaki A, Yamada K, Suga J, Otaka A, Kuzuya H . 1998 J. Biol. Chem. 273: 940–944
Ku NO, Liao J, Omary MB . 1998 EMBO J. 17: 1892–1906
Kumagai A, Dunphy WG . 1999 Genes Dev. 13: 1067–1072
Laronga C, Yang HY, Neal C, Lee MH . 2000 J. Biol. Chem. 275: 23106–23112
Layfield R, Fergusson J, Aitken A, Lowe J, Landon M, Mayer RJ . 1996 Neurosci Lett. 209: 57–60
Lee KH, Harrington MG . 1997 Electrophoresis 18: 502–506
Li W, Skoulakis EM, Davis RL, Perrimon N . 1997 Development 124: 4163–4171
Liao J, Omary MB . 1996 J. Cell. Biol. 133: 345–357
Liu D, Bienkowska J, Petosa C, Collier RJ, Fu H, Liddington R . 1995 Nature 376: 191–194
Liu Y, Liu YC, Meller N, Giampa L, Elly C, Doyle M, Altman A . 1999 J. Immunol. 162: 7095–7101
Liu Y, Yin G, Surapisitchat J, Berk BC, Min W . 2001 J. Clin. Invest. 107: 917–923
Liu YC, Elly C, Yoshida H, Bonnefoy-Berard N, Altman A . 1996 J. Biol. Chem. 271: 14591–14595
Liu YC, Liu Y, Elly C, Yoshida H, Lipkowitz S, Altman A . 1997 J. Biol. Chem. 272: 9979–9985
Lopez-Girona A, Furnari B, Mondesert O, Russell P . 1999 Nature 397: 172–175
Luo Z, Tzivion G, Belshaw PJ, Vavvas D, Marshall M, Avruch J . 1996 Nature 383: 181–185
Luo ZJ, Zhang XF, Rapp U, Avruch J . 1995 J. Biol. Chem. 270: 23681–23687
Marshall CJ . 1996 Nature 383: 127–128
Masters SC, Pederson KJ, Zhang L, Barbieri JT, Fu H . 1999 Biochemistry 38: 5216–5221
Megidish T, Cooper J, Zhang L, Fu H, Hakomori S . 1998 J. Biol. Chem. 273: 21834–21845
Megidish T, White T, Takio K, Titani K, Igarashi Y, Hakomori S . 1995 Biochem. Biophys. Res. Commun. 216: 739–747
Michaud NR, Fabian JR, Mathes KD, Morrison DK . 1995 Mol. Cell. Biol. 15: 3390–3397
Mils V, Baldin V, Goubin F, Pinta I, Papin C, Waye M, Eychene A, Ducommun B . 2000 Oncogene 19: 1257–1265
Muller WE, Laplanche JL, Ushijima H, Schroder HC . 2000 Mech. Ageing Dev. 116: 193–218
Muslin AJ, Tanner JW, Allen PM, Shaw AS . 1996 Cell 84: 889–897
Muslin AJ, Xing H . 2000 Cell Signal 12: 703–709
Nagata K, Puls A, Futter C, Aspenstrom P, Schaefer E, Nakata T, Hirokawa N, Hall A . 1998 EMBO J. 17: 149–158
Nakanishi K, Hashizume S, Kato M, Honjoh T, Setoguchi Y, Yasumoto K . 1997 Hum. Antibodies 8: 189–194
Obsil T, Ghirlando R, Klein DC, Ganguly S, Dyda F . 2001 Cell 105: 257–267
Ogihara T, Isobe T, Ichimura T, Taoka M, Funaki M, Sakoda H, Onishi Y, Inukai K, Anai M, Fukushima Y, Kikuchi M, Yazaki Y, Oka Y, Asano T . 1997 J. Biol. Chem. 272: 25267–25274
Pallas DC, Fu H, Haehnel LC, Weller W, Collier RJ, Roberts TM . 1994 Science 265: 535–537
Pan S, Sehnke PC, Ferl RJ, Gurley WB . 1999 Plant Cell. 11: 1591–1602
Pawson T, Nash P . 2000 Genes Dev. 14: 1027–1047
Pawson T, Scott JD . 1997 Science 278: 2075–2080
Peng CY, Graves PR, Thoma RS, Wu Z, Shaw AS, Piwnica-Worms H . 1997 Science 277: 1501–1555
Perego L, Berruti G . 1997 Mol. Reprod. Dev. 47: 370–379
Pietromonaco SF, Seluja GA, Aitken A, Elias L . 1996 Blood Cells Mol. Dis. 22: 225–237
Reuther GW, Fu H, Cripe LD, Collier RJ, Pendergast AM . 1994 Science 266: 129–133
Rittinger K, Budman J, Xu J, Volinia S, Cantley LC, Smerdon SJ, Gamblin SJ, Yaffe MB . 1999 Mol. Cell. 4: 153–166
Roberts MR . 2000 Curr. Opin. Plant. Biol. 3: 400–405
Roberts RL, Mosch HU, Fink GR . 1997 Cell 89: 1055–1065
Robinson K, Jones D, Patel Y, Martin H, Madrazo J, Martin S, Howell S, Elmore M, Finnen MJ, Aitken A . 1994 Biochem. J. 299: 853–861
Rosenquist M, Sehnke P, Ferl RJ, Sommarin M, Larsson C . 2000 J. Mol. Evol. 51: 446–458
Seimiya H, Sawada H, Muramatsu Y, Shimizu M, Ohko K, Yamane K, Tsuruo T . 2000 EMBO J. 19: 2652–2661
Shaw A . 2000 Curr. Biol. 10: R400
Shoji M, Kawamoto S, Setoguchi Y, Mochizuki K, Honjoh T, Kato M, Hashizume S, Hanagiri T, Yoshimatsu T, Nakanishi K. et al. 1994 Hum. Antibodies Hybridomas 5: 123–130
Skoulakis EM, Davis RL . 1996 Neuron 17: 931–944
Skoulakis EM, Davis RL . 1998 Mol. Neurobiol. 16: 269–284
Suzuki H, Itoh F, Toyota M, Kikuchi T, Kakiuchi H, Imai K . 2000 Cancer Res. 60: 4353–4357
Tang SJ, Suen TC, McInnes RR, Buchwald M . 1998 J. Biol. Chem. 273: 25356–25363
Thorson JA, Yu LW, Hsu AL, Shih NY, Graves PR, Tanner JW, Allen PM, Piwnica-Worms H, Shaw AS . 1998 Mol. Cell. Biol. 18: 5229–5238
Tien AC, Hsei HY, Chien CT . 1999 Mech. Dev. 81: 209–212
Todd A, Cossons N, Aitken A, Price GB, Zannis-Hadjopoulos M . 1998 Biochemistry 37: 14317–14325
Tzivion G, Luo Z, Avruch J . 1998 Nature 394: 88–92
Tzivion G, Luo ZJ, Avruch J . 2000 J. Biol. Chem. 275: 29772–29778
Van Der Hoeven PC, Van Der Wal JC, Ruurs P, Van Dijk MC, Van Blitterswijk J . 2000 Biochem. J. 345: 297–306
van Zeijl MJ, Testerink C, Kijne JW, Wang M . 2000 FEBS Lett. 473: 292–296
Vercoutter-Edouart AS, Lemoine J, Le Bourhis X, Louis H, Boilly B, Nurcombe V, Revillion F, Peyrat JP, Hondermarck H . 2001 Cancer Res. 61: 76–80
Villaret DB, Wang T, Dillon D, Xu J, Sivam D, Cheever MA, Reed SG . 2000 Laryngoscope 110: 374–381
Vincenz C, Dixit VM . 1996 J. Biol. Chem. 271: 20029–20034
Wang AH, Kruhlak MJ, Wu J, Bertos NR, Vezmar M, Posner BI, Bazett-Jones DP, Yang XJ . 2000a Mol. Cell. Biol. 20: 6904–6912
Wang B, Yang H, Liu YC, Jelinek T, Zhang L, Ruoslahti E, Fu H . 1999 Biochemistry 38: 12499–12504
Wang H, Zhang L, Liddington R, Fu H . 1998 J. Biol. Chem. 273: 16297–16304
Wang W, Shakes DC . 1996 J. Mol. Evol. 43: 384–398
Wang Y, Jacobs C, Hook KE, Duan H, Booher RN, Sun Y . 2000b Cell Growth Differ. 11: 211–219
Waterman MJ, Stavridi ES, Waterman JL, Halazonetis TD . 1998 Nat. Genet. 19: 175–178
Weiner H, Kaiser WM . 1999 FEBS Lett. 455: 75–78
Xiao B, Smerdon SJ, Jones DH, Dodson GG, Soneji Y, Aitken A, Gamblin SJ . 1995 Nature 376: 188–191
Xing H, Zhang S, Weinheimer C, Kovacs A, Muslin AJ . 2000 EMBO J. 19: 349–358
Yaffe MB, Rittinger K, Volinia S, Caron PR, Aitken A, Leffers H, Gamblin SJ, Smedron SJ, Cantley LC . 1997 Cell 91: 961–971
Yaffe MB, Cantley LC . 1999 Nature 402: 30–31
Yaffe MB, Elia AE . 2001 Curr. Opin. Cell. Biol. 13: 131–138
Yang J, Winkler K, Yoshida M, Kornbluth S . 1999 EMBO J. 18: 2174–2183
Zeidler M . 2000 Ann. Neurol. 47: 683–684
Zeng Y, Forbes KC, Wu Z, Moreno S, Piwnica-Worms H, Enoch T . 1998 Nature 395: 507–510
Zha J, Harada H, Yang E, Jockel J, Korsmeyer SJ . 1996 Cell 87: 619–628
Zhang L, Chen J, Fu H . 1999a Proc. Natl. Acad. Sci. USA 96: 8511–8515
Zhang L, Wang H, Liu D, Liddington R, Fu H . 1997 J. Biol. Chem. 272: 13717–13724
Zhang S, Xing H, Muslin AJ . 1999b J. Biol. Chem. 274: 24865–24872
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We thank Joseph Avruch for helpful discussions during the preparation of the manuscript.
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Tzivion, G., Shen, Y. & Zhu, J. 14-3-3 proteins; bringing new definitions to scaffolding. Oncogene 20, 6331–6338 (2001). https://doi.org/10.1038/sj.onc.1204777
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