Disease relevance of CycD

• In differentiating eyes, CycD-Cdk4 caused cell enlargement (hypertrophy) in post-mitotic cells [1].
• In undifferentiated proliferating wing imaginal cells, CycD-Cdk4 caused accelerated cell division (hyperplasia) without affecting cell cycle phasing or cell size [1].
• In this issue of Developmental Cell, Frei and Edgar reveal that Cyclin D/Cdk4-stimulated growth requires Hph, a prolyl hydroxylase that is a key component of a cell's ability to respond to hypoxia [2].

High impact information on CycD

• Hedgehog regulates cell growth and proliferation by inducing Cyclin D and Cyclin E [3].
• Upregulation of Cyclin D expression by Hh mediates the distinct ability of Hh to promote cellular growth [3].
• We show here that mRpL12 is required for CycD/Cdk4-induced cell growth [4].
• The Drosophila melanogaster cyclin-dependent protein kinase complex CycD/Cdk4 stimulates both cell cycle progression and cell growth (accumulation of mass) [4].
• The cellular response to CycD-Cdk4-driven growth varied according to cell type [1].

Biological context of CycD

• In endoreplicating salivary gland cells, CycD-Cdk4 caused excessive DNA replication and cell enlargement (hypertrophy) [1].
• Since Hph's hydroxylation activity depends on oxygen and possibly the mitochondrial activity, these data provide a link between CycD/Cdk4 and oxygen/energy homeostasis [5].
• Isolation of Drosophila cyclin D, a protein expressed in the morphogenetic furrow before entry into S phase [6].
• The role of RBF in developmentally regulated cell proliferation in the eye disc and in Cyclin D/Cdk4 induced cellular growth [7].

Other interactions of CycD

• 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 [8].
• A breath of fresh air for cyclin D/Cdk4: triggering growth via Hph [2].
• Drosophila cyclin D/Cdk4 requires Hif-1 prolyl hydroxylase to drive cell growth [8].
• Here we describe phenotypic consequences of null mutations in Cyclin D, the single D-type cyclin gene in Drosophila [9].
• Studies of tumor cells show that the p16(ink4a)/cdk4/cyclin D/pRB pathway is mutated in most forms of cancer, suggesting that the deregulation of E2F, and hence the cell cycle, is a common event in tumorigenesis [10].

References