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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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Blood 98, 636-642
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Biol Reprod 64, 654-665
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S. Goodbourn, L. Didcock, and R. E. Randall (2000)
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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Endocrinology 141, 3422-3429
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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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C. Contursi, I-M. Wang, L. Gabriele, M. Gadina, J. O'Shea, H. C. Morse III, and K. Ozato (2000)
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A. C. Ward, I. Touw, and A. Yoshimura (2000)
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S. Oh, Y. Song, J. Yim, and T. K. Kim (1999)
J. Biol. Chem. 274, 37473-37478
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J. Biol. Chem. 274, 36351-36356
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J. Biol. Chem. 274, 35492-35498
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The V Protein of Simian Virus 5 Inhibits Interferon Signalling by Targeting STAT1 for Proteasome-Mediated Degradation.
L. Didcock, D. F. Young, S. Goodbourn, and R. E. Randall (1999)
J. Virol. 73, 9928-9933
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Inhibition of Interleukin 2 Signaling and Signal Transducer and Activator of Transcription (STAT)5 Activation during T Cell Receptor-mediated Feedback Inhibition of T Cell Expansion.
I.-H. Lee, W. P. Li, K. B. Hisert, and L. B. Ivashkiv (1999)
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T. Kim, T. Y. Kim, Y.-H. Song, I. M. Min, J. Yim, and T. K. Kim (1999)
J. Biol. Chem. 274, 30686-30689
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J. Virol. 73, 8469-8475
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L.-M. Ting, A. C. Kim, A. Cattamanchi, and J. D. Ernst (1999)
J. Immunol. 163, 3898-3906
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Blood 94, 1782-1789
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Cloning of Interferon-Stimulated Gene 17: The Promoter and Nuclear Proteins That Regulate Transcription.
D. J. Perry, K. J. Austin, and T. R. Hansen (1999)
Mol. Endocrinol. 13, 1197-1206
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Functional Roles of STAT Family Proteins: Lessons from Knockout Mice.
S. Akira (1999)
Stem Cells 17, 138-146
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C. Venkataraman, S. Leung, A. Salvekar, H. Mano, and U. Schindler (1999)
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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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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   Abstract »    Full Text »    PDF »
Rapid inhibition of interleukin-6 signaling and Stat3 activation mediated by mitogen-activated protein kinases.
T. K. Sengupta, E. S. Talbot, P. A. Scherle, and L. B. Ivashkiv (1998)
PNAS 95, 11107-11112
   Abstract »    Full Text »    PDF »
p130, p107, and pRb Are Differentially Regulated in Proliferating Cells and during Cell Cycle Arrest by alpha -Interferon.
N. S. B. Thomas, A. R. Pizzey, S. Tiwari, C. D. Williams, and J. Yang (1998)
J. Biol. Chem. 273, 23659-23667
   Abstract »    Full Text »    PDF »
Inhibition of Stat1-mediated gene activation by PIAS1.
B. Liu, J. Liao, X. Rao, S. A. Kushner, C. D. Chung, D. D. Chang, and K. Shuai (1998)
PNAS 95, 10626-10631
   Abstract »    Full Text »    PDF »
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
   Abstract »    Full Text »    PDF »
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
   Abstract »    Full Text »
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
   Abstract »    Full Text »
Di-leucine-mediated Internalization of Ligand by a Truncated Growth Hormone Receptor Is Independent of the Ubiquitin Conjugation System.
R. Govers, P. van Kerkhof, A. L. Schwartz, and G. J. Strous (1998)
J. Biol. Chem. 273, 16426-16433
   Abstract »    Full Text »    PDF »
Oncogenic Abl and Src tyrosine kinases elicit the ubiquitin-dependent degradation of target proteins through a Ras-independent pathway.
Z. Dai, R. C. Quackenbush, K. D. Courtney, M. Grove, D. Cortez, G. W. Reuther, and A. M. Pendergast (1998)
Genes & Dev. 12, 1415-1424
   Abstract »    Full Text »
Characterization of a Second Member of the Sentrin Family of Ubiquitin-like Proteins.
T. Kamitani, K. Kito, H. P. Nguyen, T. Fukuda-Kamitani, and E. T. H. Yeh (1998)
J. Biol. Chem. 273, 11349-11353
   Abstract »    Full Text »    PDF »
Interleukin-3-Induced Activation of the JAK/STAT Pathway Is Prolonged by Proteasome Inhibitors.
B. A. Callus and B. Mathey-Prevot (1998)
Blood 91, 3182-3192
   Abstract »    Full Text »    PDF »
Ubiquitination Is Required for the Retro-translocation of a Short-lived Luminal Endoplasmic Reticulum Glycoprotein to the Cytosol for Degradation by the Proteasome.
M. de Virgilio, H. Weninger, and N. E. Ivessa (1998)
J. Biol. Chem. 273, 9734-9743
   Abstract »    Full Text »    PDF »
Prolonged STAT1 Activation Related to the Growth Arrest of Malignant Lymphoma Cells by Interferon-alpha.
P. M. Grimley, H. Fang, H. Rui, E. F. Petricoin III, S. Ray, F. Dong, K. H. Fields, R. Hu, K. C. Zoon, S. Audet, et al. (1998)
Blood 91, 3017-3027
   Abstract »    Full Text »    PDF »
Desensitization of the Growth Hormone-Induced Janus Kinase 2 (Jak 2)/Signal Transducer and Activator of Transcription 5 (Stat5)-Signaling Pathway Requires Protein Synthesis and Phospholipase C.
L. Fernandez, A. Flores-Morales, O. Lahuna, D. Sliva, G. Norstedt, L.-A. Haldosen, A. Mode, and J.-A. Gustafsson (1998)
Endocrinology 139, 1815-1824
   Abstract »    Full Text »    PDF »


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