Canonical and non-canonical JAK-STAT signaling.
Aberrant activation of the JAK-STAT pathway has been implicated in many human cancers. It has widely been assumed that the effects of STAT activation are mediated by direct transcriptional induction of STAT target genes. However, recent findings in Drosophila have identified a non-canonical mode of JAK-STAT signaling, which directly controls heterochromatin stability. This indicates that the JAK-STAT pathway also controls cellular epigenetic status, which affects expression of genes beyond those under direct STAT transcriptional control. Given the evolutionary conservation of the canonical pathway among different species, the non-canonical mode of JAK-STAT signaling might also operate in vertebrates. In this review, canonical versus non-canonical JAK-STAT signaling and the implications for gene regulation and cancer formation are discussed.
Li
Willis X
WX
Department of Biomedical Genetics, University of Rochester Medical Center, 601 Elmwood Avenue, KMRB 2-9641, Rochester, NY 14642, USA. willis_li@urmc.rochester.edu
D000818:Animals; D001773:Blood Cells / Q000166:cytology / Q000378:metabolism; D049109:Cell Proliferation; D000090266:Chromobox Protein Homolog 5; D002868:Chromosomal Proteins, Non-Histone / Q000378:metabolism*; D004330:Drosophila / Q000378:metabolism; D029721:Drosophila Proteins / Q000378:metabolism*; D044127:Epigenesis, Genetic; D006570:Heterochromatin / Q000378:metabolism; D006801:Humans; D053612:Janus Kinases / Q000378:metabolism*; D009369:Neoplasms / Q000378:metabolism; D050791:STAT Transcription Factors / Q000378:metabolism*; D015398:Signal Transduction
D002868:Chromosomal Proteins, Non-Histone; D029721:Drosophila Proteins; D006570:Heterochromatin; D050791:STAT Transcription Factors; D000090266:Chromobox Protein Homolog 5; D053612:Janus Kinases