Unphosphorylated STATs go nuclear.
The JAK/STAT signal transduction pathway has traditionally been viewed as a cytokine-stimulated activator of gene expression consisting of a straightforward receptor/JAK kinase/STAT transcription factor cascade. Recent studies in Drosophila, have, however consistently identified a range of chromatin-remodelling factors as regulators of in vivo JAK/STAT signalling. Now, the detailed analysis of one of these, heterochromatin protein 1 (HP1), has provided an insight into an unexpected non-canonical in vivo role for STAT. In this model, unphosphorylated STATs associate with and maintain the stability of transcriptionally repressed heterochromatin--an effect countered by the recruitment of STAT to the canonical pathway. We examine the background of this new model and its implications for JAK/STAT pathway requirements in stem cell maintenance and cancer.
Brown
Stephen
S
Faculty of Life Science, Michael Smith Building, Oxford Road, Manchester M13 9PT, UK.
Zeidler
Martin P
MP
D000818:Animals; D002454:Cell Differentiation; D002467:Cell Nucleus / Q000235:genetics / Q000378:metabolism*; D042002:Chromatin Assembly and Disassembly; D002868:Chromosomal Proteins, Non-Histone / Q000378:metabolism / Q000502:physiology; D004330:Drosophila / Q000235:genetics / Q000378:metabolism*; D029721:Drosophila Proteins / Q000378:metabolism / Q000502:physiology; D005786:Gene Expression Regulation; D019337:Hematologic Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D008957:Models, Genetic; D010766:Phosphorylation; D050791:STAT Transcription Factors / Q000378:metabolism* / Q000502:physiology; D015398:Signal Transduction; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism
D002868:Chromosomal Proteins, Non-Histone; D029721:Drosophila Proteins; D050791:STAT Transcription Factors; C452193:heterochromatin protein 1, Drosophila