Stat3 activity is required for centrosome duplication in chinese hamster ovary cells.
The centrosome is the major microtubule organizing center in mammalian cells. During interphase, the single centrosome is duplicated and the progeny centrosomes then serve as the spindle poles during mitosis. Little is known about the signals that drive centrosome doubling. In these studies, various inhibitors and molecular approaches were used to demonstrate a role for the Stat pathway in regulating the events of centrosome doubling. Both piceatannol and a dominant negative behaving Stat3 adenovirus were able to disrupt centrosome duplication in hydroxyurea-arrested Chinese hamster ovary cells, demonstrating that Stat3 is a key signaling molecule in the events of centrosome duplication. Investigation into the role of Stat3 signaling during centrosome production demonstrated that Stat3 does not directly regulate the transcription of the centrosome genes encoding gamma-tubulin and PCM-1. Instead, Stat3 apparently regulated gamma-tubulin levels through post-transcriptional mechanisms whereas PCM-1 levels actually increased when Stat3 was inhibited, suggesting more complex mechanisms for regulating PCM-1 production. These studies demonstrate that Stat3 plays a vital role in centrosome duplication events, although the downstream targets of Stat3 activation leading to centrosome production remain to be established. The proposed signaling pathway utilizes Stat3 as a fundamental signaling molecule that directs the production of the various centrosome proteins indirectly.
Department of Cell Biology and Neuroscience, Department of Pharmacology, and Center for Lung Biology, University of South Alabama, Mobile, Alabama 36688, USA.
Brandon
B
Metge
Solomon
S
Ofori-Acquah
Troy
T
Stevens
Ron
R
Balczon
D000818:Animals; D016466:CHO Cells / Q000166:cytology*; D002453:Cell Cycle; D018797:Cell Cycle Proteins / Q000032:analysis; D018385:Centrosome / Q000502:physiology*; D006224:Cricetinae; D004268:DNA-Binding Proteins / Q000502:physiology*; D008870:Microtubules; D050796:STAT3 Transcription Factor; D015398:Signal Transduction; D013267:Stilbenes / Q000494:pharmacology; D015534:Trans-Activators / Q000502:physiology*; D014404:Tubulin / Q000032:analysis
D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D050796:STAT3 Transcription Factor; D013267:Stilbenes; D015534:Trans-Activators; D014404:Tubulin; C041525:3,3',4,5'-tetrahydroxystilbene