Abl oncogene bypasses normal regulation of Jak/STAT activation.
In normal cells, the strength and duration of proliferative signaling pathways are tightly regulated. In oncogenic settings, negative regulation is often bypassed to allow constitutive activation of these pathways. In our recent manuscript, we identify a mechanism that allows the v-Abl oncogene to bypass negative regulation by SOCS-1 to constitutively activate Jak-Stat signaling. The mechanism involves post-translational modifications of SOCS-1 that disrupt its interaction with the proteasome, thereby preventing it from targeting activated Jak kinases for degradation. In this review, we discuss the implications of these findings for our understanding of v-Abl oncogenesis and the regulation of SOCS protein function.
Limnander
André
A
Integrated Program in Cellular, Molecular and Biophysical Studies, Columbia University College of Physicians and Surgeons, New York, New York USA.
Rothman
Paul B
PB
D000818:Animals; D005786:Gene Expression Regulation; D053613:Janus Kinase 1; D016374:Oncogene Proteins v-abl / Q000235:genetics* / Q000378:metabolism*; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D050794:STAT1 Transcription Factor / Q000378:metabolism*; D015398:Signal Transduction; D050826:Suppressor of Cytokine Signaling Proteins / Q000378:metabolism
D016374:Oncogene Proteins v-abl; D050794:STAT1 Transcription Factor; D050826:Suppressor of Cytokine Signaling Proteins; D011505:Protein-Tyrosine Kinases; D053613:Janus Kinase 1