TY - JOUR
T1 - DNA replication stalling attenuates tyrosine kinase signaling to suppress S phase progression
AU - Shields, Benjamin James
AU - Hauser, Christine
AU - Bukczynska, Patricia Evelina
AU - Court, Naomi Wynne
AU - Tiganis, Tony
PY - 2008
Y1 - 2008
N2 - Here we report that T cell protein tyrosine phosphatase (TCPTP)-dependent and -independent pathways attenuate the JAK and Src protein tyrosine kinases (PTKs) and STAT3 phosphorylation to suppress cyclin D1 expression and S phase progression in response to DNA replication stress. Cells that lack TCPTP fail to suppress JAK1, Src, and STAT3, allowing for sustained cyclin D1 levels and progression through S phase despite continued replication stress. Cells that bypass the checkpoint undergo aberrant mitoses with lagging chromosomes that stain for the DNA damage marker ?H2AX. Therefore, inactivating JAK, Src, and STAT3 signaling pathways in response to DNA replication stress may be essential for the suppression of S phase progression and the maintenance of genomic stability.
AB - Here we report that T cell protein tyrosine phosphatase (TCPTP)-dependent and -independent pathways attenuate the JAK and Src protein tyrosine kinases (PTKs) and STAT3 phosphorylation to suppress cyclin D1 expression and S phase progression in response to DNA replication stress. Cells that lack TCPTP fail to suppress JAK1, Src, and STAT3, allowing for sustained cyclin D1 levels and progression through S phase despite continued replication stress. Cells that bypass the checkpoint undergo aberrant mitoses with lagging chromosomes that stain for the DNA damage marker ?H2AX. Therefore, inactivating JAK, Src, and STAT3 signaling pathways in response to DNA replication stress may be essential for the suppression of S phase progression and the maintenance of genomic stability.
UR - http://www.ncbi.nlm.nih.gov/pubmed/18691551
M3 - Article
SN - 1535-6108
VL - 14
SP - 166
EP - 179
JO - Cancer Cell
JF - Cancer Cell
IS - 2
ER -