Medical College of Wisconsin
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A small amphipathic alpha-helical region is required for transcriptional activities and proteasome-dependent turnover of the tyrosine-phosphorylated Stat5. EMBO J 2000 Feb 01;19(3):392-9

Date

02/02/2000

Pubmed ID

10654938

Pubmed Central ID

PMC305576

DOI

10.1093/emboj/19.3.392

Scopus ID

2-s2.0-0034142208   99 Citations

Abstract

Cytokines induce the tyrosine phosphorylation and associated activation of signal transducers and activators of transcription (Stat). The mechanisms by which this response is terminated are largely unknown. Among a variety of inhibitors examined, the proteasome inhibitors MG132 and lactacystin affected Stat4, Stat5 and Stat6 turnover by significantly stabilizing the tyrosine-phosphorylated form. However, these proteasome inhibitors did not affect downregulation of the tyrosine-phosphorylated Stat1, Stat2 and Stat3. With Stat5 isoforms, we have observed that tyrosine-phosphorylated carboxyl-truncated forms of Stat5 proteins were considerably more stable than phosphorylated wild-type forms of the protein. Also, the C-terminal region of Stat5 could confer proteasome-dependent downregulation to Stat1. With a series of C-terminal deletion mutants, we have defined a relatively small, potentially amphipathic alpha-helical region that is required for the rapid turnover of the phosphorylated Stat5 proteins. The region is also required for transcriptional activation, suggesting that the functions are linked. The results are consistent with a model in which the transcriptional activation domain of activated Stat5 is required for its transcriptional activity and downregulation through a proteasome-dependent pathway.

Author List

Wang D, Moriggl R, Stravopodis D, Carpino N, Marine JC, Teglund S, Feng J, Ihle JN

Author

Demin Wang PhD Assistant Professor in the Microbiology and Immunology department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Acetylcysteine
Animals
Cell Line
Cysteine Endopeptidases
Cysteine Proteinase Inhibitors
DNA-Binding Proteins
Leupeptins
Milk Proteins
Multienzyme Complexes
Phosphorylation
Phosphotyrosine
Proteasome Endopeptidase Complex
Protein Structure, Secondary
STAT5 Transcription Factor
Trans-Activators
Transcriptional Activation
Tyrosine
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