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Science 20 September 1996:
Vol. 273. no. 5282, pp. 1717 - 1719
DOI: 10.1126/science.273.5282.1717
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Reports

Regulation of Interferon-gamma -Activated STAT1 by the Ubiquitin-Proteasome Pathway

Tae Kook Kim and Tom Maniatis *

STAT proteins (signal transducers and activators of transcription) are latent cytoplasmic transcription factors that are phosphorylated by Janus kinases in response to cytokines. Phosphorylated STAT proteins translocate to the nucleus, where they transiently turn on specific sets of cytokine-inducible genes. The mechanism that controls the amounts of activated STAT proteins is not understood. STAT1 proteins activated by interferon-gamma treatment in HeLa cells were shown to be stabilized by a proteasome inhibitor and ubiquitinated in vivo. Thus, the amount of activated STAT1 may be negatively regulated by the ubiquitin-proteasome pathway.

Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA 02138, USA.
*   To whom correspondence should be addressed.

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J. Immunol. 167, 1469-1481
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Blood 98, 636-642
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Blood 97, 3860-3866
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P. Najarro, P. Traktman, and J. A. Lewis (2001)
J. Virol. 75, 3185-3196
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Bovine Interferon-{{tau}} Stimulates the Janus Kinase-Signal Transducer and Activator of Transcription Pathway in Bovine Endometrial Epithelial Cells.
M. Binelli, P. Subramaniam, T. Diaz, G. A. Johnson, T. R. Hansen, L. Badinga, and W. W. Thatcher (2001)
Biol Reprod 64, 654-665
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J. Gen. Virol. 81, 2341-2364
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Z. Tian, X. Shen, H. Feng, and B. Gao (2000)
J. Immunol. 165, 3959-3965
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J. L. Turgeon and D. W. Waring (2000)
Endocrinology 141, 3422-3429
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Endocrinology 141, 2090-2097
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Inducible NF-kappa B Activation Is Permitted by Simultaneous Degradation of Nuclear Ikappa Balpha.
P. Renard, Y. Percherancier, M. Kroll, D. Thomas, J.-L. Virelizier, F. Arenzana-Seisdedos, and F. Bachelerie (2000)
J. Biol. Chem. 275, 15193-15199
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J. Schmitz, M. Weissenbach, S. Haan, P. C. Heinrich, and F. Schaper (2000)
J. Biol. Chem. 275, 12848-12856
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H. Daino, I. Matsumura, K. Takada, J. Odajima, H. Tanaka, S. Ueda, H. Shibayama, H. Ikeda, M. Hibi, T. Machii, et al. (2000)
Blood 95, 2577-2585
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RNase-L-dependent Destabilization of Interferon-induced mRNAs. A ROLE FOR THE 2-5A SYSTEM IN ATTENUATION OF THE INTERFERON RESPONSE.
X.-L. Li, J. A. Blackford, C. S. Judge, M. Liu, W. Xiao, D. V. Kalvakolanu, and B. A. Hassel (2000)
J. Biol. Chem. 275, 8880-8888
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Insulin-Like Growth Factor I-Induced Degradation of Insulin Receptor Substrate 1 Is Mediated by the 26S Proteasome and Blocked by Phosphatidylinositol 3'-Kinase Inhibition.
A. V. Lee, J. L. Gooch, S. Oesterreich, R. L. Guler, and D. Yee (2000)
Mol. Cell. Biol. 20, 1489-1496
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c-Kit triggers dual phosphorylations, which couple activation and degradation of the essential melanocyte factor Mi.
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S. Oh, Y. Song, J. Yim, and T. K. Kim (1999)
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B. J. Roberts and M. L. Whitelaw (1999)
J. Biol. Chem. 274, 36351-36356
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V.-A. T. Nguyen and B. Gao (1999)
J. Biol. Chem. 274, 35492-35498
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L. Didcock, D. F. Young, S. Goodbourn, and R. E. Randall (1999)
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I.-H. Lee, W. P. Li, K. B. Hisert, and L. B. Ivashkiv (1999)
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Activation of Interferon Regulatory Factor 3 in Response to DNA-damaging Agents.
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J. Biol. Chem. 274, 30686-30689
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Expression of Hepatitis C Virus Proteins Inhibits Signal Transduction through the Jak-STAT Pathway.
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J. Virol. 73, 8469-8475
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Mycobacterium tuberculosis Inhibits IFN-{gamma} Transcriptional Responses Without Inhibiting Activation of STAT1.
L.-M. Ting, A. C. Kim, A. Cattamanchi, and J. D. Ernst (1999)
J. Immunol. 163, 3898-3906
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Cellular Physiology of STAT3: Where's the Cytoplasmic Monomer?.
M. I. Ndubuisi, G. G. Guo, V. A. Fried, J. D. Etlinger, and P. B. Sehgal (1999)
J. Biol. Chem. 274, 25499-25509
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The Proteasome Inhibitor PS-341 in Cancer Therapy.
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J. Immunol. 162, 4053-4061
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Proteasome-dependent degradation of the human estrogen receptor.
Z. Nawaz, D. M. Lonard, A. P. Dennis, C. L. Smith, and B. W. O'Malley (1999)
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Z. Nawaz, D. M. Lonard, C. L. Smith, E. Lev-Lehman, S. Y. Tsai, M.-J. Tsai, and B. W. O'Malley (1999)
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Stimulation of Stat5 by Granulocyte Colony-Stimulating Factor (G-CSF) Is Modulated by Two Distinct Cytoplasmic Regions of the G-CSF Receptor.
F. Dong, X. Liu, J. P. de Koning, I. P. Touw, L. Henninghausen, A. Larner, and P. M. Grimley (1998)
J. Immunol. 161, 6503-6509
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Amino-terminal Signal Transducer and Activator of Transcription (STAT) Domains Regulate Nuclear Translocation and STAT Deactivation.
I. Strehlow and C. Schindler (1998)
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Rapid inhibition of interleukin-6 signaling and Stat3 activation mediated by mitogen-activated protein kinases.
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B. Liu, J. Liao, X. Rao, S. A. Kushner, C. D. Chung, D. D. Chang, and K. Shuai (1998)
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A Janus Kinase Inhibitor, JAB, Is an Interferon-gamma -Inducible Gene and Confers Resistance to Interferons.
H. Sakamoto, H. Yasukawa, M. Masuhara, S. Tanimura, A. Sasaki, K. Yuge, M. Ohtsubo, A. Ohtsuka, T. Fujita, T. Ohta, et al. (1998)
Blood 92, 1668-1676
   Abstract »    Full Text »    PDF »
Characterization of a Nerve Growth Factor-Inducible Cellular Activity That Enhances Herpes Simplex Virus Type 1 Gene Expression and Replication of an ICP0 Null Mutant in Cells of Neural Lineage.
R. Jordan, J. Pepe, and P. A. Schaffer (1998)
J. Virol. 72, 5373-5382
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Identification and Characterization of a Constitutively Active STAT5 Mutant That Promotes Cell Proliferation.
M. Onishi, T. Nosaka, K. Misawa, A. L.-F. Mui, D. Gorman, M. McMahon, A. Miyajima, and T. Kitamura (1998)
Mol. Cell. Biol. 18, 3871-3879
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Antigen receptor signaling induces MAP kinase-mediated phosphorylation and degradation of the BCL-6 transcription factor.
H. Niu, B. H. Ye, and R. Dalla-Favera (1998)
Genes & Dev. 12, 1953-1961
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