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Originally published as MBC in Press, 10.1091/mbc.E07-03-0263 on July 18, 2007

Vol. 18, Issue 10, 3733-3740, October 2007

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putzig Is Required for Cell Proliferation and Regulates Notch Activity in DrosophilaFormula

Sabrina J. Kugler, and Anja C. Nagel

Institute of Genetics (240), University of Hohenheim, 70599 Stuttgart, Germany

Submitted March 21, 2007; Revised July 3, 2007; Accepted July 10, 2007
Monitoring Editor: Carl-Henrik Heldin

We have identified the gene putzig (pzg) as a key regulator of cell proliferation and of Notch signaling in Drosophila. pzg encodes a Zn-finger protein that was found earlier within a macromolecular complex, including TATA-binding protein-related factor 2 (TRF2)/DNA replication-related element factor (DREF). This complex is involved in core promoter selection, where DREF functions as a transcriptional activator of replication-related genes. Here, we provide the first in vivo evidence that pzg is required for the expression of cell cycle and replication-related genes, and hence for normal developmental growth. Independent of its role in the TRF2/DREF complex, pzg acts as a positive regulator of Notch signaling that may occur by chromatin activation. Down-regulation of pzg activity inhibits Notch target gene activation, whereas Hedgehog (Hh) signal transduction and growth regulation are unaffected. Our findings uncover different modes of operation of pzg during imaginal development of Drosophila, and they provide a novel mechanism of Notch regulation.

This was published online ahead of print in MBC in Press (http://www.molbiolcell.org/cgi/doi/10.1091/mbc.E07-03-0263) on July 18, 2007.

Formula The online version of this article contains supplemental material at MBC Online (http://www.molbiolcell.org).

Address correspondence to: Anja C. Nagel (anjnagel{at}uni-hohenheim.de)






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