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The Drosophila mitochondrial ribosomal protein mRpL12 is required for Cyclin D/Cdk4‐driven growth
Author(s) -
Frei Christian,
Galloni Mireille,
Hafen Ernst,
Edgar Bruce A
Publication year - 2005
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1038/sj.emboj.7600523
Subject(s) - biology , microbiology and biotechnology , e2f , cell growth , cyclin dependent kinase 4 , cell cycle , cyclin d , drosophila melanogaster , kinase , cyclin , cyclin dependent kinase 2 , genetics , gene , protein kinase a
The Drosophila melanogaster cyclin‐dependent protein kinase complex CycD/Cdk4 stimulates both cell cycle progression and cell growth (accumulation of mass). CycD/Cdk4 promotes cell cycle progression via the well‐characterized RBF/E2F pathway, but our understanding of how growth is stimulated is still limited. To identify growth regulatory targets of CycD/Cdk4, we performed a loss‐of‐function screen for modifiers of CycD/Cdk4‐induced overgrowth of the Drosophila eye. One mutation that suppressed CycD/Cdk4 was in a gene encoding the mitochondrial ribosomal protein, mRpL12. We show here that mRpL12 is required for CycD/Cdk4‐induced cell growth. Cells homozygous mutant for mRpL12 have reduced mitochondrial activity, and exhibit growth defects that are very similar to those of cdk4 null cells. CycD/Cdk4 stimulates mitochondrial activity, and this is mRpL12 dependent. H if‐1 p rolyl h ydroxylase (Hph), another effector of CycD/Cdk4, regulates growth and is required for inhibition of the hypoxia‐inducible transcription factor 1 (Hif‐1). Both functions depend on mRpL12 dosage, suggesting that CycD/Cdk4, mRpL12 and Hph function together in a common pathway that controls cell growth via affecting mitochondrial activity.