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Dev Cell. 2004 Feb;6(2):241-51.

Drosophila cyclin D/Cdk4 requires Hif-1 prolyl hydroxylase to drive cell growth.

Author information

1
Division of Basic Sciences, Fred Hutchinson Cancer Research Center, P.O. Box 19024, Seattle, WA 98109, USA. christian.frei@zool.unizh.ch

Abstract

The Drosophila cyclin-dependent protein kinase complex Cyclin D/Cdk4 induces cell growth (accumulation of mass) as well as proliferation (cell cycle progression). To understand how CycD/Cdk4 promotes growth, we performed a screen for modifiers of CycD/Cdk4-driven overgrowth in the eye. Loss-of-function mutations in Hif-1 prolyl hydroxylase (Hph), an enzyme involved in the cellular response to hypoxic stress, dominantly suppress the growth but not the proliferation function of CycD/Cdk4. hph mutant cells are defective for growth, and, remarkably, ectopic expression of Hph is sufficient to increase cellular growth. Epistasis analysis places Hph downstream of CycD/Cdk4. Overexpressed CycD/Cdk4 causes an increase in Hph protein in tissues where Hph induces growth, suggesting a mechanism whereby Hph levels are regulated posttranscriptionally in response to CycD/Cdk4. Our data suggest that Hph, in addition to its function in hypoxic response, is a regulator of cellular growth and that it is a key mediator for CycD/Cdk4.

PMID:
14960278
DOI:
10.1016/s1534-5807(03)00409-x
[Indexed for MEDLINE]
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