Disease relevance of Cdk4

• 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].

High impact information on Cdk4

• The Drosophila melanogaster cyclin-dependent protein kinase complex CycD/Cdk4 stimulates both cell cycle progression and cell growth (accumulation of mass) [2].
• The Drosophila mitochondrial ribosomal protein mRpL12 is required for Cyclin D/Cdk4-driven growth [2].
• Our results indicate, therefore, that progression into and through the cell cycle can occur in the absence of Cdk4 [3].
• These results suggest that the ability of Cyclin D/Cdk4 to drive growth in the proliferating wing cells is distinct from that in the none-dividing eye cells or the ability of activated Ras to induce growth, and that RBF may have a role in regulating growth in the proliferating wing discs [4].
• Therefore, we have analyzed whether the developmentally controlled inactivation of Cyclin E-Cdk2 required for the epidermal cell proliferation arrest occurs as a consequence of Cyclin D-Cdk4 inactivation [5].

Biological context of Cdk4

• They demonstrate that Cyclin D-Cdk4 does not function as the master regulator of the embryonic cell proliferation program [5].
• In endoreplicating salivary gland cells, CycD-Cdk4 caused excessive DNA replication and cell enlargement (hypertrophy) [1].
• As previously observed with null mutations in the single Drosophila Cdk4 gene, these mutations do not primarily affect progression through the G1 phase [6].
• 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 [7].
• New work in Drosophila demonstrates that cdk4 loss causes phenotypes similar to the loss of JAK/STAT pathway components [8].

Anatomical context of Cdk4

• Cells homozygous mutant for mRpL12 have reduced mitochondrial activity, and exhibit growth defects that are very similar to those of cdk4 null cells [2].

Other interactions of Cdk4

• In DROSOPHILA:, single genes for Cyclin D and Cdk4 have been identified, simplifying genetic analysis [3].
• However, the growth of cells and of the organism is reduced in Cdk4 mutants, indicating a role of D-type cyclin-dependent protein kinases in the modulation of growth rates [3].
• Epistasis analysis places Hph downstream of CycD/Cdk4 [9].
• These results demonstrate a new function for Cdk4 and a new mode of STAT activation [8].
• Specific genetic interactions between Cdk4 and hop mutations suggest that Cdk4 functions downstream of the HOP tyrosine kinase [10].

References