Abstract
Stat3 mediates cellular responses associated with proliferation, survival and differentiation, but the mechanisms underlying the diverse effects of this signaling molecule remain unknown. M1 mouse myeloid leukemia cells arrest growth and differentiate into macrophages following treatment with interleukin 6 (IL-6) or leukemia inhibitory factor (LIF), and recent studies have shown that Stat3 plays a central role in this process. Utilizing representational difference analysis, we demonstrate that expression of the mouse BATF gene is upregulated as an early response to IL-6/LIF stimulation and Stat3 activation in this cell system. Immunoblots using antibodies to BATF detected an increase in BATF protein in response to LIF/IL-6 stimulation. BATF is a member of the AP-1 family of basic leucine zipper transcription factors and functions to inhibit the transcriptional and biological functions of AP-1 activity in mammalian cells. BATF forms complexes with c-Jun in M1 cells and forced expression of BATF in the absence of Stat3 signaling results in a reduced rate of cellular growth. These results indicate that Stat3 mediates cellular growth by modulating AP-1 activity through the induction of BATF.
Similar content being viewed by others
References
Aronheim A, Zandi E, Hennemann H, Elledge SJ, Karin M . 1997 Mol. Cell. Biol. 17: 3094–3102
Bellido T, O'Brien CA, Roberson PK, Manolagas SC . 1998 J. Biol. Chem. 273: 21137–21144
Bromberg JF, Wrzeszczynska MH, Devgan G, Zhao Y, Pestell RG, Albanese C, Darnell JE . 1999 Cell 98: 295–303
Dorsey MJ, Tae HJ, Sollenberger KG, Mascarenhas NT, Johansen LM, Taparowsky EJ . 1995 Oncogene 11: 2255–2265
Echlin DR, Tae HJ, Mitin N, Taparowsky EJ . 2000 Oncogene 19: 1752–1763
Fukada T, Hibi M, Yamanaka Y, Takahashi-Tezuka M, Fujitani Y, Yamaguchi T, Nakajima K, Hirano T . 1996 Immunity 5: 449–460
Fukada T, Ohtani T, Yoshida Y, Shirogane T, Nishida K, Nakajima K, Hibi M, Hirano T . 1998 EMBO J. 17: 6670–6677
Hirano T, Ishihara K, Hibi M . 2000 Oncogene 19: 2548–2556
Hubank M, Schatz DG . 1994 Nucleic Acids Res. 22: 5640–5648
Kitamura T, Morikawa Y . 2000 Methods Mol. Biol. 134: 143–152
Lisitsyn N, Lisitsyn N, Wigler M . 1993 Science 259: 946–951
Lord KA, Abdollahi A, Hoffman-Liebermann B, Liebermann DA . 1993 Mol. Cell. Biol. 13: 841–851
Masuhara M, Sakamoto H, Matsumoto A, Suzuki R, Yasukawa H, Mitsui K, Wakioka T, Tanimura S, Sasaki A, Misawa H, Yokouchi M, Ohtsubo M, Yoshimura A . 1997 Biochem. Biophys. Res. Commun. 239: 439–446
Matsuda T, Nakamura T, Nakao K, Arai T, Katsuki M, Heike T, Yokota T . 1999 EMBO J. 18: 4261–4269
O'Farrell AM, Parry DA, Zindy F, Roussel MF, Lees E, Moore KW, Mui AL . 2000 J. Immunol. 164: 4607–4615
Ohtani T, Ishihara K, Atsumi T, Nishida K, Kaneko Y, Miyata T, Itoh S, Narimatsu M, Maeda H, Fukada T, Itoh M, Okano H, Hibi M, Hirano T . 2000 Immunity 12: 95–105
Selvakumaran M, Liebermann DA, Hoffman-Liebermann B . 1992 Mol. Cell. Biol. 12: 2493–2500
Senga T, Iwamoto T, Kitamura T, Miyake Y, Hamaguchi M . 2001 J. Biol. Chem. 276: 32678–32681
Shimozaki K, Nakajima K, Hirano T, Nagata S . 1997 J. Biol. Chem. 272: 25184–25189
Shirogane T, Fukada T, Muller JM, Shima DT, Hibi M, Hirano T . 1999 Immunity 11: 709–719
Takahashi-Tezuka M, Yoshida Y, Fukada T, Ohtani T, Yamanaka Y, Nishida K, Nakajima K, Hibi M, Hirano T . 1998 Mol. Cell. Biol. 18: 4109–4117
Williams KL, Nanda I, Lyons GE, Kuo CT, Schmid M, Leiden JM, Kaplan MH, Taparowsky EJ . 2001 Eur. J. Immunol. 5: 1620–1627
Acknowledgements
This work was supported by grants-in-aid for COE Research from the Ministry of Japan Society for promotion of Science and by PHS award CA78264 to EJ Taparowsky.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Senga, T., Iwamoto, T., Humphrey, S. et al. Stat3-dependent induction of BATF in M1 mouse myeloid leukemia cells. Oncogene 21, 8186–8191 (2002). https://doi.org/10.1038/sj.onc.1205918
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/sj.onc.1205918
- Springer Nature Limited
Keywords
This article is cited by
-
Increased BATF expression is associated with the severity of liver damage in patients with chronic hepatitis B
Clinical and Experimental Medicine (2018)
-
Increased expression of the Th17-IL-6R/pSTAT3/BATF/RorγT-axis in the tumoural region of adenocarcinoma as compared to squamous cell carcinoma of the lung
Scientific Reports (2014)
-
Specificity through cooperation: BATF–IRF interactions control immune-regulatory networks
Nature Reviews Immunology (2013)
-
Functional interaction between Envoncogene from Jaagsiekte sheep retrovirus and tumor suppressor Sprouty2
Retrovirology (2010)
-
Batf
AfCS-Nature Molecule Pages (2010)