The different functions of Stat5 and chromatin alteration through Stat5 proteins.
Stat5 proteins modulate gene transcription upon cytokine- and growth factor action. Stat5a and Stat5b proteins alone are weak activators of transcription. They can modify chromatin organization through oligomerization and they act predominantly in co-operation and interaction with other proteins. The conservative view of exclusively nuclear functions of Stat5 was challenged by the observation of additional Stat5 effects in the cytoplasm, resulting in activation of the PI3K-Akt pathway. We summarize biological consequences of mutations in conserved domains of Stat5 or of deletions in the N- or C-terminal domains with impact on target gene transcription. Formation of higher-order oligomers is dramatically changed upon amino- or carboxyterminal deletions in Stat5 proteins. Mutations in or deletion of the Stat5 N-terminus leads to diminished leukemogenic potential of oncogenic Stat5, probably due to the inability to form Stat5 tetramers. The Stat5 N-terminal domain prevents persistent activation and can act as a DNA-docking platform for the glucocorticoid receptor (GR). The corresponding protocols should facilitate follow-up studies on Stat5 proteins and their contribution to normal physiological versus pathological processes through differential chromatin binding.
Ludwig Boltzmann Institute for Cancer Research, Vienna, Austria.
Jan-Wilhelm
JW
Kornfeld
Florian
F
Grebien
Marc A
MA
Kerenyi
Katrin
K
Friedbichler
Boris
B
Kovacic
Barbara
B
Zankl
Andrea
A
Hoelbl
Harini
H
Nivarti
Hartmut
H
Beug
Veronika
V
Sexl
Mathias
M
Muller
Lukas
L
Kenner
Ernst W
EW
Mullner
Fabrice
F
Gouilleux
Richard
R
Moriggl
D000818:Animals; D001327:Autoimmune Diseases / Q000503:physiopathology; D002843:Chromatin / Q000502:physiology*; D004247:DNA / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000503:physiopathology; D051379:Mice; D018345:Mice, Knockout; D023421:Models, Animal; D009196:Myeloproliferative Disorders / Q000503:physiopathology; D009369:Neoplasms / Q000503:physiopathology; D020033:Protein Isoforms / Q000502:physiology; D050799:STAT5 Transcription Factor / Q000172:deficiency / Q000235:genetics / Q000502:physiology*
D002843:Chromatin; D020033:Protein Isoforms; D050799:STAT5 Transcription Factor; D004247:DNA