Abstract
The study, addressed to explore the transcriptional expression and regulation of Apoptosis-antagonizing transcription factor (AATF) gene within various types of human leukemic cell lines, revealed that AATF gene was overexpressed ubiquitously in all the leukemic cell lines studied and this upregulation was accompanied by c-myc gene overamplification in these cells. Downregulation of AATF gene transcription within leukemic cells not only resulted in the downregulation of c-myc gene and vice-versa but also contributed to apoptosis leading to cell death. Further, the link between AATF expression and leukemic cellular apoptosis involved PI3K/Akt pathway. Based on these results we propose that AATF gene may be of crucial importance in maintaining the leukemic state of a cell compartment through its ability to initiate cell proliferation coupled with repression of cellular apoptosis.
References
Kaul D Receptor Ck and leukemogenesis. Leukemia Res, 22: 389–394, 1998
Burgdorf S, Leister P, Scheidtmann KH TSG101 interacts with apoptosis antagonizing transcription factor and enhances androgen receptor-mediated transcription by promoting its monoubiquitination. J Biol Chem 279: 17524–17534, 2004
Bruno T, De Angelis R, De Nicola F, Barbato C, Di Padova M, Corbi N, Libri V, Benassi B, Mattei E, Chersi A, Soddu S, Floridi A, Passananti C, Fanciulli M Che-1 affects cell growth by interacting with the recruitment of HDAC-1 by Rb Cancer cell, 2: 387–399, 2002
Page G, Lodige I, Kogel D, Scheidtmann KH AATF, a novel transcription factor that interacts with DLK/ZIP kinase FEBS Lett, 462: 187–191, 1999
Di Padova M, Bruno T, De Nicola F, Iezzi S, D’Angelo C, Gallo R, Nicosia D, Corbi N, Biroccio A, Floridi A, Passananti C, Fanciulli M Che-1 arrests human carcinoma cell proliferation by displacing HDAC-1 from the p21WAF1/C1P1 promoter J Biol Chem, 278: 36496–36504, 2003
Moller MB Molecular control of the cell cycle in cancer: biological and clinical aspects Dan Med Bull, 50(2): 118–138, 2003
Preuss U, Landsberg G, Scheidtmann KH Novel mitosis-specific phosphorylation of histone H3 at Thr11 mediated by Dlk/ZIP kinase Nucleic Acids Res, 31(3): 878–885, 2003
Palmieri C, Coombes RC, Vigushin DM Targeted histone deacetylase inhibition for cancer prevention and therapy Prog Drug Res: 63, 147–181, 2005
Downward J Mechanisms and consequences of activation of protein kinase B/ Akt Curr Opin Cell Biol, 10: 262–267, 1998
Kaul D, Rani R, Sehgal R Receptor-Ck regulates giardia encystations process Mol Cell Biochem, 225: 167–169, 2001
Anand PK, Kaul D, Sharma M Green tea polyphenol inhibits Mycobacterium tuberculosis survival within human macrophages Int J Biochem Cell Biol, 38: 600–609, 2006
Sikand K, Kaul D, Varma N Receptor Ck-dependent signaling regulates hTERT gene transcription BMC Cell Biol, 7: 2–22, 2006
Kaul D, Anand PK Regulation of PPAR-γ gene in human promyelocytic HL-60 cell line Leukemia Res, 27: 683–686, 2003
Albert T, Wells J, Funk JO, Pullner A, Raschke EE, Stelzer G, Meisterernst M, Farnham PJ, Eick D The chromatin structure of the dual c-myc promoter p1/p2 is regulated by separate elements J Biol Chem, 276: 20482–20490, 2001
Evan GI, Vousden KH Proliferation, cell cycle and apoptosis in cancer Nature, 411: 342–348, 2001
Kasibhatla S, Tseng B Why target apoptosis in cancer treatment. Mol Cancer Ther, 2: 573–580, 2003
Cheema KS, Mishra SK, Rangnekar VM, Tari AM, Kumar R, Lopez-Berestein G Par-4 transcriptionally regulates BCL-2 through a WT1-binding site on the bcl-2 promoter J Biol Chem, 278(22): 19995–20005, 2003
Goswami A, Burikhanov R, de Thonel A, Fujita N, Goswami M, Zhao Y, Eriksson JE, Tsuruo T, Rangnekar VM Binding and phosphorylation of par-4 by Akt is essential for cancer cell survival Mol Cell 20(1): 33–44, 2005
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Kaul, D., Mehrotra, A. Functional characterization of AATF transcriptome in human leukemic cells. Mol Cell Biochem 297, 215–220 (2007). https://doi.org/10.1007/s11010-006-9317-1
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11010-006-9317-1