DNA replication stalling attenuates tyrosine kinase signaling to suppress S phase progression

Benjamin James Shields, Christine Hauser, Patricia Evelina Bukczynska, Naomi Wynne Court, Tony Tiganis

Research output: Contribution to journalArticleResearchpeer-review

49 Citations (Scopus)

Abstract

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.
Original languageEnglish
Pages (from-to)166 - 179
Number of pages14
JournalCancer Cell
Volume14
Issue number2
Publication statusPublished - 2008

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