Abstract
Previous work has demonstrated that lineage-specific transcription factors play essential roles in red blood cell development. More recent studies have shown that these factors participate in critical protein-protein interactions in addition to binding DNA. The zinc finger transcription factor GATA-1, a central mediator of erythroid gene expression, interacts with multiple proteins including FOG-1, EKLF, SP1, CBP/p300 and PU.1. The mechanisms by which these interactions influence GATA-1 function, as well as any possible relationships between these seemingly disparate complexes, remain incompletely understood. However, several new findings have provided further insight into the functional significance of some of these interactions. Studies involving point mutants of GATA-1 have shown that a direct physical interaction between GATA-1 and FOG-1 is essential for normal human erythroid and megakaryocyte maturation in vivo. In addition, evidence has emerged that physical interaction between GATA-1 and the myeloid/lymphoid specific factor PU.1, an oncogene implicated in murine erythroleukemia, acts to functionally cross-antagonize one another. This provides a possible mechanism by which dysregulated expression of hematopoietic transcription factors leads to lineage maturation arrest in leukemias.
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References
Adams B, Dorfler P, Aguzzi A, Kozmik Z, Urbanek P, Maurer-Fogy I, Busslinger M . 1992 Genes Dev. 6: 1589–1607
Armstrong JA, Bieker JJ, Emerson BM . 1998 Cell 95: 93–104
Bash RO, Hall S, Timmons CF, Crist WM, Amylon M, Pullen J, Carrol AJ, Buchanan GR, Smith RG, Baer R . 1993 Blood 86: 666–676
Begley CG, Aplan PD, Denning SM, Haynes BF, Waldmann TA, Kirsch IR . 1989 Proc. Natl. Acad. Sci. USA 86: 10128–10132
Blobel GA, Nakajima T, Eckner R, Montminy M, Orkin SH . 1998 Proc. Natl. Acad. Sci. USA 95: 2061–2066
Boyes J, Byfield P, Nakatani Y, Ogryzko V . 1998 Nature 396: 594–598
Brownlie A, Donovan A, Pratt SJ, Paw BH, Oates AC, Brugnara C, Witkowska HE, Sassa S, Zon LI . 1998 Nat. Genet. 20: 244–250
Chen Q, Cheng J-T, Tsai L-H, Schneider N, Buchanan G, Carroll A, Crist W, Ozanne B, Siciliano MJ, Baer R . 1990 EMBO J. 9: 415–424
Coghill E, Eccleston S, Fox V, Cerruti L, Brown C, Cunningham J, Jane S, Perkins A . 2001 Blood 97: 1861–1868
Crispino JD, Lodish M, Mackay JP, Orkin SH . 1999 Mol. Cell 3: 219–228
Crispino JD, Lodish Maya, Thurberg BL, Litovsky SH, Collins T, Molkentin JD, Orkin SH . 2001 Genes Dev. 15: 839–844
Donovan A, Brownlie A, Zhou Y, Shepard J, Pratt SJ, Moynihan J, Paw BH, Drejer A, Barut B, Zapata A, Law TC, Brugnara C, Lux SE, Pinkus GS, Pinkus JL, Kingsley PD, Palis J, Fleming MD, Andrews NC, Zon LI . 2000 Nature 403: 776–781
Evans T, Felsenfeld G . 1989 Cell 58: 877–885
Evans T, Felsenfeld G . 1991 Mol. Cell Biol. 11: 843–853
Finger LR, Kagan J, Christopher G, Kurtzberg J, Hershfield MS, Nowell PC, Croce CM . 1989 Proc. Natl. Acad. Sci. USA 86: 5039–5043
Fossett N, Tevosian SG, Gajewski K, Zhang Q, Orkin SH, Schulz RA . 2001 Proc. Natl. Acad. Sci. USA 98: 7342–7347
Fox AH, Liew C, Holmes M, Kowalski K, Mackay J, Crossley M . 1999 EMBO J. 18: 2812–2822
Fujiwara Y, Browne CP, Cunniff K, Goff SC, Orkin SH . 1996 Proc. Natl. Acad. Sci. USA 93: 12355–12358
Goodman RH, Smolik S . 2000 Genes Dev. 14: 1553–1577
Hromas R, Orazi A, Neiman RS, Maki R, Van Beveran C, Moore J, Klemsz M . 1993 Blood 82: 2998–3004
Hung H-L, Lau J, Kim AY, Weiss MJ, Blobel GA . 1999 Mol. Cell Biol. 19: 3496–3505
Ito E, Toki T, Ishihara H, Ohtani H, Gu L, Yokoyama M, Engel JD, Yamamoto M . 1993 Nature 362: 466–468
Jasinski M, Keller P, Fujiwara Y, Orkin SH, Bessler M . 2001 Blood 98: 2248–2255
Keller G, Kennedy M, Papayannopoulou T, Wiles MV . 1993 Mol. Cell. Biol. 13: 473–486
Keller G, Wall C, Fong AZC, Hawley TS, Hawley RG . 1998 Blood 92: 877–887
Kulessa H, Frampton J, Graf T . 1995 Genes Dev. 9: 1250–1262
Kung AL, Rebel VI, Bronson RT, Ch'ng L-E, Sieff CA, Livingston DM, Yao T-P . 2000 Genes Dev. 14: 272–277
Lebestky T, Chang T, Hartenstein V, Banerjee U . 2000 Science 288: 146–149
Liao EC, Paw BH, Peters LL, Zapata A, Pratt SJ, Do CP, Lieschke G, Zon LI . 2000 Development 127: 5123–5132
Lu J-R, Mckinsey TA, Xu H, Wang D-Z, Richardson JA, Olson EN . 1999 Mol. Cell. Biol. 19: 4495–4502
Martin DIK, Orkin SH . 1990 Genes Dev. 4: 1886–1898
McKercher SR, Torbett BE, Anderson KL, Henkel GW, Vestal DJ, Baribault H, Klemsz M, Feeney AJ, Wu GE, Paige CJ, Maki RA . 1996 EMBO J. 15: 5647–5658
Merika M, Orkin SH . 1995 Mol. Cell Biol. 15: 2437–2447
Miller IJ, Bieker JJ . 1993 Mol Cell Biol. 13: 2776–2786
Moreau-Gachelin F, Ray D, Mattei MG, Tambourin P, Tavitian A . 1989 Oncogene 4: 1449–1456
Moreau-Gachelin F, Wendling F, Molina T, Denis N, Titeux M, Grimber G, Briand P, Vainchenker W, Tavitian A . 1996 Mol. Cell. Biol. 16: 2453–2463
Nerlov C, Querfurth E, Kulessa H, Graf T . 2000 Blood 95: 2543–2551
Nichols KE, Crispino JD, Poncz M, White JG, Orkin SH, Maris JM, Weiss MJ . 2000 Nat. Genet. 24: 266–270
Nuez B, Michalovich D, Bygrave A, Ploemacher R, Grosveld F . 1995 Nature 375: 316–318
Nutt SL, Heavey B, Rolink AG, Busslinger M . 1999 Nature 401: 556–562
O'Neil J, Billa M, Oikemus S, Kelliher M . 2001 Oncogene 20: 3897–3905
Orkin SH, Kazazian HHJ, Antonarakis SE, Goff SC, Boehm CD, Sexton JP, Waber PG, Giardina PJ . 1982 Nature 296: 627–631
Orkin SH . 1992 Blood 80: 575–581
Osada H, Grutz G, Axelson H, Forster A, Rabbitts TH . 1995 Proc. Natl. Acad. Sci. USA 92: 9585–9589
Pabst T, Mueller BU, Harakawa N, Schoch C, Haferlach T, Behre G, Hiddemann W, Zhang D-E, Tenen DG . 2001 Nat. Med. 7: 444–451
Perkins AC, Gaensler KM, Orkin SH . 1996 Proc. Natl. Acad. Sci. USA 93: 12267–12271
Perkins AC, Sharpe AH, Orkin SH . 1995 Nature 375: 318–322
Pevny L, Simon CM, Robertson E, Klein WH, TSai SF, D'Agati V, Orkin SH, Costantini F . 1991 Nature 349: 257–260
Porcher C, Liao EC, Fujiwara Y, Zon LI, Orkin SH . 1999 Development 126: 4603–4615
Porcher C, Swat W, Rockwell K, Fujiwara Y, Alt FW, Orkin SH . 1996 Cell 86: 47–57
Querfurth E, Schuster M, Kulessa H, Crispino JD, Doderlein G, Orkin SH, Graf T, Nerlov C . 2000 Genes Dev. 14: 2515–2525
Rajewsky K, Gu H, Kuhn R, Betz UAK, Muller W, Roes J, Schwenk F . 1996 J. Clin. Invest. 98: 600–603
Rekhtman N, Radparvar F, Evans T, Skoultchi AI . 1999 Genes Dev. 13: 1398–1411
Robb L, Lyons I, Li R, Hartley L, Kontgen F, Harvey RP, Metcalf D, Begley CG . 1995 Proc. Natl. Acad. Sci. USA 92: 7075–7079
Schuetze S, Stenberg PE, Kabat D . 1993 Mol. Cell. Biol. 13: 5670–5678
Scott EW, Simon CM, Anastasi J, Singh H . 1994 Science 265: 1573–1577
Seale P, Sabourin LA, Girgis-Gabardo A, Mansouri A, Gruss P, Rudnicki MA . 2000 Cell 102: 777–786
Shivdasani RA, Fujiwara Y, McDevitt MA, Orkin SH . 1997 EMBO J. 16: 3965–3973
Shivdasani RA, Mayer E, Orkin SH . 1995 Nature 373: 432–434
Shivdasani RA, Orkin SH . 1996 Blood 87: 4025–4039
Svensson EC, Tufts RL, Polk CE, Leiden JM . 1999 Proc. Natl. Acad. Sci. USA 96: 956–961
Svensson ED, Huggins GS, Lin H, Clendenin C, Jiang F, Tufts R, Dardik FB, Leiden JM . 2000 Nat. Genet. 25: 353–356
Tevosian SG, Deconinck AE, Cantor AB, Reiff HI, Fujiwara Y, Corfas G, Orkin SH . 1999 Proc. Natl. Aca. Sci. USA 96: 950–955
Tevosian SG, Deconinck AE, Tanaka M, Schinke M, Silvio LH, Izumo S, Fujiwara Y, Orkin SH . 2000 Cell 101: 729–739
Tsai SF, Marting DIK, Zon LI, D'andrea AD, Wong GG, Orkin SH . 1989 Nature 339: 446–451
Tsang AP, Fujiwara Y, Hom DB, Orkin SH . 1998 Genes Dev. 12: 1176–1188
Tsang AP, Visvader JE, Turner AC, Fujiwara Y, Yu C, Weiss M, Crossley M, Orkin SH . 1997 Cell 90: 109–119
Visvader JE, Elefanty AG, Strasser A, Adams JM . 1992 EMBO J. 11: 4557–4564
Vyas P, Ault K, Jackson CJ, Orkin SH, Shivdasani R . 1999 Blood 93: 2867–2875
Wadman IA, Osada H, Grutz GG, Agulnick AD, Westphal H, Forster A, Rabbitts TH . 1997 EMBO J. 16: 3145–3157
Warren AJ, Colledge WH, Carlton MBL, Evans MJ, Smith AJH, Rabbitts TH . 1994 Cell 78: 45–58
Weiss MJ, Orkin SH . 1995a Exp. Hematol. 23: 99–107
Weiss MJ, Orkin SH . 1995b Proc. Natl. Acad. Sci. USA 92: 9623–9627
Wijgerde M, Gribnau J, Trimborn T, Nuez B, Philipsen S, Grosveld F, Fraser P . 1996 Genes Dev. 10: 2894–2902
Zhang P, Behre G, Pan J, Iwama A, Wara-Aswapati N, Radomska HS, Auron PE, Tenen DG, Sun Z . 1999 Proc. Natl. Acad. Sci., USA 96: 8705–8710
Zhang P, Zhang X, Iwama A, Yu C, Smith KA, Mueller BU, Narravula S, Torbett BE, Orkin SH, Tenen DG . 2000 Blood 96: 2641–2648
Acknowledgements
AB Cantor was supported by an NCI K08 Mentored Clinical Scientist Award (CA 82175-02)
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Cantor, A., Orkin, S. Transcriptional regulation of erythropoiesis: an affair involving multiple partners. Oncogene 21, 3368–3376 (2002). https://doi.org/10.1038/sj.onc.1205326
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DOI: https://doi.org/10.1038/sj.onc.1205326
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