The authorship is shared equally by Valentina Calò and Manuela Migliavacca, and their names are listed in alphabetical order.
Review Article
You have free access to this content
STAT proteins: From normal control of cellular events to tumorigenesis†
Article first published online: 31 JUL 2003
DOI: 10.1002/jcp.10364
Copyright © 2003 Wiley-Liss, Inc.
Additional Information
How to Cite
Calò, V., Migliavacca, M., Bazan, V., Macaluso, M., Buscemi, M., Gebbia, N. and Russo, A. (2003), STAT proteins: From normal control of cellular events to tumorigenesis. J. Cell. Physiol., 197: 157–168. doi: 10.1002/jcp.10364
- †
Publication History
- Issue published online: 21 AUG 2003
- Article first published online: 31 JUL 2003
- Manuscript Accepted: 17 APR 2003
- Manuscript Received: 31 MAR 2003
LITERATURE CITED
- . 2000. Roles of STAT3 defined by tissue-specific gene targeting. Oncogene 19(21): 2607–2611.
- , . 2002. A nuclear protein tyrosine phosphatase TC-PTP is a potential negative regulator of the PRL-mediated signaling pathway; dephosphorilation and deactivation of signal trasducer and activator of transcription 5a and 5b by TC-PTP in nucleus. Mol Endocrinol 16: 58–69.
- . 2000a. New therapeutic agents targeting the epidermal growth factor receptor. J Clin Oncol 18(Suppl 21): 54S–59S.
- . 2000b. Current and planned clinical trials with trastuzumab (Herceptin). Semin Oncol 27(5 Suppl 9): 27–32.
- , , . 1998. Three-dimensional structure of the STAT3b homodimer bound to DNA. Nature (Lond) 394: 145–151.
- , , , . 2000. STATs in oncogenesis. Oncogene 19(21): 2474–2488.
- , , , , , , , , , . 2001. Stat3-mediated Myc expression is required for Src transformation and PDGF-induced mitogenesis. Proc Natl Acad Sci USA 98(13): 7319–7324.
- , , . 1996. JAKs and STATs branch out. Trends Cell Biol 6: 336–340.
- . 2002. Stat proteins and oncogenesis (review). J Clin Invest 109(9): 1139–1142.
- , . 2000. The role of STATs in transcriptional control and their impact on cellular function. Oncogene 19: 2468–2473.
- , , , , . 1998. Stat3 activation is required for cellular transformation by v-src. Mol Cell Biol 18(5): 2553–2558.
- , , , , , , . 1999. Stat3 as an oncogene. Cell 98(3): 295–303.
- , , . 2002. Activated Stat signaling in human tumors provides novel molecular targets for therapeutic intervention. Clin Cancer Res 8: 945–954.
- , , , , , , , . 2000. Tel-Jak2 transgenic mice develop T-cell leukemia. Blood 95: 3891–3899.
- , , . 1999. STAT proteins as novel targets for cancer therapy. Curr Opin Oncol 11: 490–496.
- , , , , , , , , . 1999. Suppression of epithelial apoptosis and delayed mammary gland involution in mice with a conditional knockout of Stat3. Genes Dev 13: 2604–2616.
- , , . 2000a. Association of STATs with relatives and friend. Trends Cell Biol 10(3): 106–111.
- , , , . 2000b. How Stat1 mediates constitutive gene expression: A complex of unphosphorylated Stat1 and IRF1 supports transcription of LMP2 gene. EMBO J 19(15): 4111–4122.
- , , , , , . 1998. Crystal structure of a tyrosine phosphorilated Stat-1 dimer bound to DNA. Cell 93: 827–839.
- , , , . 1999. Advances in cytokine signaling: The role of Jaks and STATs (review). Transplant Proc 31: 1482–1487.
- , , , , , . 1996. Cell growth arrest and induction of cyclin-dependent kinase inhibitor p21 WAF/CIP1mediated by STAT1. Science 272(5262): 719–722.
- , , . 1998. Association and direct activation of signal transducer and activator of transcription1alpha by platelet-derived growth factor receptor. J Clin Invest 101(12): 2751–2760.
- , , , , , , . 1997. Specific inhibition of Stat3 signal transduction by PIAS3. Science 278: 1803–1805.
- , , . 2000. The role of Stats in myeloid differentiation and leukemia. Oncogene 19: 2511–2522.
- , , , . 2000. A Stat3-inter-acting protein (StIP1) regulates cytokine signal transduction. Proc Natl Acad Sci USA 97: 10120–10125.
- , . 1999. Drug resistance in multiple myeloma: Approaches to circumvention. Review. Semin Oncol 26(5 Suppl 13): 23–27.
- , , . 1995. Jak-STAT signaling induced by the v-abl oncogene. Science 269(5232): 1875–1877.
- . 1997. STATs and gene regulation. Science 277: 1630–1635.
- , , , , , . 1995. Requirement for MAPkinase (ERK2) activity in interferon alpha- and interferon beta stimulated gene expression through STAT proteins. Science 269: 1721–1723.
- , , , , . 1999. Stat5 activation by Bcr-Abl contributes to transformation of K562 leukaemia cells. Blood 94: 1108–1112.
- , , , . 2000. Stat5-dependent cyclinD1 and Bcl-xL expression in Bcr-Abl-transformed cells. Mol Cell Biol Res Commun 3(5): 299–305.
- , . 1999. Transcription factor activity of Stat proteins: Structural requirements and regulation by phosphorilation and interacting proteins. Cell Mol Life Sci 55: 1509–1522.
- , . 2000. Serine phosphorylation of STATs. Oncogene 19: 2628–2637.
- , , , , . 2003. Role of the JAK/STAT signal transduction pathway in the regulation of gene expression in CNS. Neurochem Res 28(1): 53–64.
- , , , , , , , , . 1999. IL-3 dependent regulation of Bcl-xL gene expression by STAT5 in a bone marrow derived cell line. Oncogene 18(29): 4191–4199.
- , , , . 1996. Targed distruption of the mouse Stat1 gene results in compromised innate immunity to viral disease. Cell 84: 443–450.
- , , , , , , , , , , , . 2001. Inhibition of STAT3 signaling leads to apoptosis of leukemic large granular lymphocytes and decreased Mcl-1 expression. J Clin Invest 107(3): 351–362.
- , . 1993. Transcription factor p91 interacts with the epidermal growth factor receptor and mediates activation of the c-fos gene promoter. Cell 74(6): 1135–45.
- , , , , , , , . 1998. STAT3 orchestrates contradictory signals in cytokine-induced G1 to S cell-cycle transition. EMBO J 17: 6670–6677.
- , , , , , , , , . 1997. Constitutive activation of Stat3 in fibroblasts transformed by diverse oncoproteins and in breast carcinoma cells. Cell Growth Differ 8(12): 1267–1276.
- , , , , , , , , , , , , , , . 2001. Constitutive activation of Stat3 by the Src and Jak tyrosine kinases participates in growth regulation of human breast carcinoma cells. Oncogene 20: 2499–2513.
- , , . 1999. p38 MAPkinase is required for STAT1 serine phosphorylation and trascriptional activation induced by interferon. EMBO J 18: 5601–5608.
- , , . 1998. Interleukin-4 inhibits growth and induces apoptosis in human breast cancer cells. Cell Growth Differ 6: 335–342.
- , , . 2002. STAT6 mediates interleukin-4 growth inhibition in human breast cancer cells. Neoplasia 4(4): 324–331.
- , , , , , , . 1998. Requirement of Stat3 but not Stat1 activation for epidermel growth factor receptor-mediated cell growth in vitro. J Clin Invest 102(7): 1385–1392.
- . 2000. STAT proteins and transcriptional responses to extracellular signals. TIBS 25: 496–502.
- , , , . 1996. Interactions between STAT and non-STAT proteins in the interferon stimulated gene factor 3 transcription complex. Mol Cell Biol 19: 5106–5112.
- , , , , , . 1994. An interleukine–4-induced transcription factor: IL-4 Stat. Science 265: 1701–1706.
- , , , . 2000. Constitutive activation of Stat3 oncogene product in human ovarian carcinoma cells. Gynec Oncol 79: 67–73.
- , . 2001. Co-operative effect of c-Src tyrosine kinase and Stat3 in activation of hepatocyte growth factor expression in mammary carcinoma cells. J Biol Chem 276(15): 12395–12403.
- , , , , , . 2000. The T-cell protein tyrosine phosphatase. Semin Immunol 12(4): 379–386 (review).
- . 2001. The STAT family in cytokine signaling. Curr Opin Cell Biol 13: 211–217.
- , . 2000. The Jak-STAT pathway. Mol Immunol 37: 1–11.
- , , , , , , . 1998. Stat5b is essential for natural killer cell-mediated proliferation and cytotoxit acitivy. J Exp Med 188: 2066–2074.
- , , , , . 1999. The significance of tetrameization in promoter recruitment by STAT5. Mol Cell Biol 19: 1910–1918.
- , , , , , , . 1998. Demonstration of an interferon gamma-dependent tumor surveillance system in immunocompetent mice. Proc Natl Acad Sci USA 95: 7556–7561.
- , , . 2001. Negative regulators of cytokine signaling. Int J Hematol 73: 292–298.
- , , , . 2002. Signaling through the JAK/STAT pathway, recent advances and future challenges. Gene 285: 1–24.
- , . 2001. SOCS proteins: Negative regulators of cytokine signaling. Stem Cells 19: 378–387. Direct Link:
- , , , , . 1997. Detective TNF-alpha-induced apoptosis in Stat1-null cells due to low costitutive levels of caspases. Science 278: 1630–1632.
- , . 2002. STATs: Transcriptional control and biological impact. Nat Rev 3: 651–662.
- , . 2002. What does stat3 do? J Clin Invest 9: 1143–1148.
- , , , . 1998. Cooperative binding of Stat1-2 heterodimers and ISGF3 to tandem DNA elements. Biochem J 80: 703–710.
- , , . 2000. Stat signaling in the pathogenesis and treatment of leukemias. Oncogene 19: 2496–2504.
- , , , , , . 1997. Stat5a is mandatory for adult mammary gland development and lactogenesis. Genes Dev 11: 179–186.
- , , , . 2000. The IL-2 receptor promotes lymphocytes proliferation and induction of the c-myc, bcl-2 and bcl-x genes through the transactivation domain of Stat5. J Immunol 164: 2533–2541.
- , , , , . 2001. STAT5 and Sp1 regulate the transcription of the cyclin D2 gene in response to IL-2. J Immunol 166: 1723–1729.
- , , , , , , , , . 1999. EMBO J 18: 1367–1377.
- , , , . 2002. Regulated nuclear import of the STAT1 transcription factor by direct binding of importin-α. EMBO J 21: 1754–1763.
- , , , , , , , , , , , , , , . 1996. Target disruption of the Stat1 gene in mice reveals unexpected physiologic specificità in the JaK-STAT signaling pathway. Cell 84: 431–442.
- , , , , , , , , , , , . 1996. Inhibition of acute lymphoblastic leukaemia by a Jak2 inhibitor. Nature 379: 645–648.
- , , , , . 1998. Constitutive activation of Jak-2 and Tyk-2 in a v-Src-transformed human gallbladder adenocarcinoma cell line. J Cell Physiol 175(2): 220–228. Direct Link:
- , , , . 2001. STAT3 activation is required for Asp(816) mutant c-Kit inducedtumorigenicity. Oncogene 20(33): 4528–4536.
- , , , , , , , , , , , , , , , , . 2002. Constitutive Stat3 activity up-regulates VEGF expression and tumor angiogenesis. Oncogene 21(13): 2000–2008.
- , , , , , . 1999. STAT5 as a molecular regulator of proliferation, differentiation and apoptosis in hematopoietic cells. EMBO J 18(17): 4754–4765.
- , , , , . 2000. Collaboration of signal transducer and activator of transcription 1 (STAT1) and BRCA1 in differential regulation of IFN-g target genes. Proc Natl Acad Sci USA 97(10): 5208–5213.
- , , , , , . 1995. Phosphorylation and activation of the DNA binding activity of purified Stat1 by the Janus protein-tyrosine kinases and the epidermal growth factor receptor. J Biol Chem 270(35): 20775–20780.
- , , , , , , . 2000. Regulation of c-myc expression by IFN-γ through Stat1-dependent and -independent pathways. EMBO J 19: 263–272.
- , , , , . 2001. PIASy, a nuclear matrix-associated SUMO E3 ligase, represses LEF1 activity by sequestration into nuclear bodies. Genes Dev 15: 3088–3103.
- , , , , , , , , . 1999. Keratinocyte-specific ablation of Stat3 exhibits impaired skin remodeling, but does not affect skin morphognesis. EMBO J 18: 4657–4668.
- , , , . 2002. Constitutive activation of Stat3alpha in brain tumors: Localization to tumor endothelial cells and activation by the endothelial tyrosine kinase receptor (VEGFR-2). Oncogene 21(13): 2058–2065.
- . 2002. Series Introduction: Jak-STAT signaling in human disease. J Clin Invest 109(9): 1133–1137.
- , , , , , , . 2001. MEN2A-RET-induced cellular transformation by activation of STAT3. Oncogene 20(38): 5350–5358.
- , , , , , , , , , , , , , , . 2000. Stat5 is essential for the myelo- and lymphoproliferative disease induced by TEL/JAK2. Mol Cell 6(3): 693–704.
- , , , , , , , , , , , . 1998. Transformation of hematopoietic cell lines to growth-factor independence and induction of a fatal myelo- and lymphoproliferative disease in mice by retrovirally transduced TEL/JAK2 fusion genes. EMBO J 17(18): 5321–5333.
- . 1999. The STAT family of proteins in cytokine signaling. Prog Biophys Mol Biol 71: 405–422.
- . 2000. Modulation of STAT signaling by STAT-interacting proteins. Oncogene 19: 2638–2644.
- , , , , . 1996. Costitutive activation of Stat5 by the Bcr-Abl oncogene in chronic myelogenous leukemia. Oncogene 13: 247–254.
- , , , , , , . 1999. Erythropoietin can induce the expression of bcl-x(L) through Stat5 in erythropoietin-dependent progenitor cell lines. J Biol Chem 274(32): 22165–22169.
- , , , , . 2002. The T cell protein tyrosine phosphatase is a negative regulator of Janus family kinases 1 and 3. Curr Biol 12: 446–453.
- , , , , , , . 2000. Induction of p21WAF1/CIP1 and cyclin D1 expression by the Src oncoprotein in mouse fibroblast: Role of activated Stat3 signaling. Oncogene 19: 5419–5427.
- , . 1998. Expression of v-src in mammary epithelial cells induces transcription via STAT3. Biochem J 331(Pt2): 381–385.
- , , , , . 1999. Fetal anemia and apoptosis of red cell progenitors in Stat5a-/-5b-/- mice: A direct role for Stat5 in Bcl-X(L) induction. Cell 98: 181–191.
- , . 2000. Stat signaling in head and neck cancer. Oncogene 19: 2489–2495.
- , , , , , . 2002. Constitutive activation of STAT3 and STAT5 is induced by leukemic fusion proteins with protein tyrosine kinase activity and is sufficient for trasformation of hematopoietic precursor cells. Exp Hematol 30: 262–271.
- , , , , . 1998. How cells respond to interferons. Ann Rev Biochem 67: 227–264.
- , . 1999. Negative regulation of theJAK/STAT pathway. Bioessays 21: 47–52. Direct Link:
- , . 2000. STAT family of transcription factors in cytokine-mediated biological responses (Mini review). Cytokine Growth Factor Rev 11: 199–207.
- , , , , , , , . 1997. Targed distruption of the mouse Stat3 gene to early embryonic lethality. Proc Natl Acad Sci USA 94: 2607–2611.
- , , , , , , , , , . 1998. Stat5a and Stat5b proteins have essential and non essential, or redundant, roles in cytokine responses. Cell 93: 841–850.
- , , , , , , . 2002. Identification of a nuclear Stat1 protein tyrosine phosphatase. Mol Cell Biol 22(16): 5662–5668.
- , , , , , , , , , , . 1996. Requirement for Stat4 in IL-12 mediated responses of natural killer and T-cells. Nature 382: 171–174.
- , , , , , . 1998. Stat3 activation by Src induces specific gene regulation and is required for cell transformation. Mol Cell Biol 18: 2545–2552.
- , , , , , , , , , . 2001. Phosphotyrosyl peptides block Stat3-mediated DNA-binding activity, gene regulation, and cell transformation. J Biol Chem 276: 45443–45455.
- , , , , , , , . 1997. Requirement of Stat5b for sexual dimorphism of body growth rates and liver gene expression. Proc Natl Acad Sci USA 94: 7239–7244.
- , , , , , , , , , , . 2000. Anticancer efficacy of the irreversible EGFr tyrosine kinase inhibitor PD 0169414 against human tumor xenografts. Cancer Chemother Pharmacol 45(3): 231–238.
- , , , , , , , . 2000. A small amphipathic alpha-helical region is required for transcriptional activities and proteasome-dependent turnover of the tyrosine-phosphorylated Stat5. EMBO J 19: 392–399.
- . 1999. Serpentine receptors and STAT activation: More than one way to twin a STAT. Trends Biochem Sci 9: 333–334.
- . 2000. STAT signaling in cell proliferation and in development. Curr Opin Genet Dev 10: 503–507.
- , , , . 2003. Control mechanism of JAK/STAT signal transduction pathway. FEBS Letters 534: 190–196.
- , , . 1999. Shp-2 tyrosine phosphatase functions as a negative regulator of the interferon-stimulated JAK-STAT pathway. Mol Cell Biol 19: 2416–2424.
- , , . 2000. Cytosolic tyrosin dephosphorylation of STAT5. JBC 275(1): 599–604.
- , , , , , , , , . 2000. Activation of Stat3 in v-Src-transformed fibroblasts requires cooperation of Jak1 kinase activity. J Biol Chem 275(32): 24935–24944.

1097-4652/asset/JCP_left.gif?v=1&s=55bd21dc6c29ea5f5b29e4649eaeb334c7805008)
