Tescalcin is an essential factor in megakaryocytic differentiation associated with Ets family gene expression.
We show here that the process of megakaryocytic differentiation requires the presence of the recently discovered protein tescalcin. Tescalcin is dramatically upregulated during the differentiation and maturation of primary megakaryocytes or upon PMA-induced differentiation of K562 cells. This upregulation requires sustained signaling through the ERK pathway. Overexpression of tescalcin in K562 cells initiates events of spontaneous megakaryocytic differentiation, such as expression of specific cell surface antigens, inhibition of cell proliferation, and polyploidization. Conversely, knockdown of this protein in primary CD34+ hematopoietic progenitors and cell lines by RNA interference suppresses megakaryocytic differentiation. In cells lacking tescalcin, the expression of Fli-1, Ets-1, and Ets-2 transcription factors, but not GATA-1 or MafB, is blocked. Thus, tescalcin is essential for the coupling of ERK cascade activation with the expression of Ets family genes in megakaryocytic differentiation.
Levay
Konstantin
K
Department of Molecular and Cellular Pharmacology and Neuroscience Program, University of Miami Miller School of Medicine, Miami, Florida 33101-6189, USA. k.levay@miami.edu
Slepak
Vladlen Z
VZ
D018952:Antigens, CD34 / Q000378:metabolism; D001854:Bone Marrow Cells / Q000378:metabolism; D002135:Calcium-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D002448:Cell Adhesion; D002454:Cell Differentiation; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D004789:Enzyme Activation; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D016023:Integrins / Q000378:metabolism; D008533:Megakaryocytes / Q000166:cytology* / Q000378:metabolism*; D015240:Phorbol 12,13-Dibutyrate / Q000494:pharmacology; D019038:Platelet Glycoprotein GPIb-IX Complex / Q000378:metabolism; D010980:Platelet Membrane Glycoproteins / Q000378:metabolism; D011123:Polyploidy; D019098:Telomerase / Q000145:classification* / Q000235:genetics* / Q000378:metabolism; D014158:Transcription, Genetic / Q000235:genetics
D018952:Antigens, CD34; D002135:Calcium-Binding Proteins; D016023:Integrins; D019038:Platelet Glycoprotein GPIb-IX Complex; D010980:Platelet Membrane Glycoproteins; C486009:TESC protein, human; C032193:glycoprotein receptor GPIb-IX; D015240:Phorbol 12,13-Dibutyrate; D048049:Extracellular Signal-Regulated MAP Kinases; D019098:Telomerase
Science. 1996 Apr 12;272(5259):263-7
8602510
Blood. 1996 Jun 1;87(11):4678-85
8639837
Proc Natl Acad Sci U S A. 1996 Mar 5;93(5):1935-40
8700862
J Biol Chem. 1996 Aug 2;271(31):18554-60
8702504
Blood. 1996 Sep 15;88(6):2071-80
8822926
Cell Growth Differ. 1996 Nov;7(11):1525-34
8930402
Acta Haematol. 1997;97(1-2):13-21
8980606
Blood. 1997 Jan 15;89(2):483-92
9002950
Mol Cell Biol. 1997 Apr;17(4):1947-58
9121442
J Biol Chem. 1997 Sep 12;272(37):23366-70
9287350
J Biol Chem. 1997 Sep 26;272(39):24300-7
9305885
Blood. 1997 Nov 1;90(9):3462-70
9345030
Leukemia. 2002 Apr;16(4):683-92
11960350
Bioessays. 2002 Jul;24(7):625-36
12111723
J Biol Chem. 2002 Dec 13;277(50):48333-41
12359731
Mol Cell Biol. 2003 May;23(10):3427-41
12724402
Blood. 2003 Jun 1;101(11):4333-41
12576332
Biochemistry. 2003 Jun 24;42(24):7448-56
12809501
Immunity. 2003 Jul;19(1):33-45
12871637
Biochemistry. 2003 Dec 16;42(49):14553-65
14661968
Nat Med. 2004 Mar;10(3):299-304
14966519
Mol Cell Biol. 2004 May;24(10):4534-45
15121870
J Clin Invest. 2004 Jul;114(1):77-84
15232614
Blood. 1973 Sep;42(3):413-21
4125240
Blood. 1981 Feb;57(2):287-97
7448424
Prog Clin Biol Res. 1983;134:277-92
6665002
J Clin Invest. 1985 Aug;76(2):431-8
3875629
Leuk Res. 1987;11(9):807-15
3478529
Blood. 1989 Jul;74(1):145-51
2473794
Blood. 1989 Sep;74(4):1196-212
2669995
Immunity. 1997 Nov;7(5):609-18
9390685
Oncogene. 1997 Dec 18;15(25):3091-102
9444957
Exp Cell Res. 1998 Feb 1;238(2):407-14
9473349
J Biol Chem. 1998 Mar 27;273(13):7572-8
9516460
Blood. 1999 Nov 15;94(10):3366-80
10552946
J Cell Physiol. 2002 Jan;190(1):7-20
11807806
J Leukoc Biol. 2002 Apr;71(4):545-56
11927640
J Clin Invest. 1990 Apr;85(4):1072-84
2318965
Trends Biochem Sci. 1998 Jun;23(6):213-6
9644975
Exp Cell Res. 1998 Jul 10;242(1):315-27
9665829
J Virol. 1998 Nov;72(11):8463-71
9765382
Eur J Biochem. 1998 Dec 1;258(2):879-89
9874259
Nature. 1999 Mar 4;398(6722):80-4
10078534
Blood. 1999 Apr 15;93(8):2637-44
10194443
J Biol Chem. 2004 Dec 10;279(50):52183-90
15466856
Proc Natl Acad Sci U S A. 2005 Mar 29;102(13):4735-40
15781852
Curr Opin Hematol. 2005 May;12(3):197-202
15867575
J Biol Chem. 2005 May 6;280(18):18008-14
15746104
J Biol Chem. 2005 Aug 12;280(32):29186-93
15941720
Mol Cell Biol. 2000 Jan;20(1):91-103
10594012
Blood. 2000 Feb 1;95(3):745-55
10648382
Nat Genet. 2000 Jun;25(2):217-22
10835641
Mol Cell Biol. 2000 Aug;20(15):5643-52
10891501
Exp Hematol. 2000 Jul;28(7):802-14
10907642
Immunity. 2000 Aug;13(2):167-77
10981960
Stem Cells. 1998;16 Suppl 2:97-106
11012182
J Biol Chem. 2000 Nov 3;275(44):34114-21
10926935
Endocrinology. 2001 Jan;142(1):455-63
11145610
Oncogene. 2000 Dec 18;19(55):6432-42
11175359
Oncogene. 2000 Dec 18;19(55):6503-13
11175366
Oncogene. 2000 Dec 18;19(55):6533-48
11175369
Int J Hematol. 2001 Jan;73(1):78-83
11372759
Curr Opin Neurobiol. 2001 Jun;11(3):312-9
11399429
Cell Growth Differ. 2001 Aug;12(8):435-45
11504709
FEBS Lett. 2001 Nov 2;507(3):331-5
11696366
Nat Rev Mol Cell Biol. 2001 Nov;2(11):827-37
11715049
Blood. 2002 Feb 1;99(3):888-97
11806991
J Cell Sci. 1992 Mar;101 ( Pt 3):671-9
1522149
Mol Cell Biol. 1993 Jan;13(1):668-76
8417360
Blood. 1993 Mar 1;81(5):1214-21
8443382
J Biol Chem. 1993 Jul 25;268(21):15847-53
8340409
J Biol Chem. 1993 Oct 15;268(29):21606-12
8408012
Genomics. 1994 Mar 1;20(1):5-12
8020956
Nature. 1995 Feb 16;373(6515):620-3
7854419
J Biol Chem. 1995 Oct 13;270(41):24532-9
7592671
Blood. 1995 Nov 15;86(10):3783-8
7579345