Disease relevance of CycE

• Atypical PKCiota contributes to poor prognosis through loss of apical-basal polarity and cyclin E overexpression in ovarian cancer [1].

Psychiatry related information on CycE

• Cyclin E at the centre of an identity crisis [2].

High impact information on CycE

• Yorkie is known to activate Cyclin E (CycE) and the apoptosis inhibitor DIAP1 [3].
• Hpo phosphorylates and activates Wts, which in turn, through unknown mechanisms, negatively regulates the transcription of cell-cycle and cell-death regulators such as cycE and diap1 [4].
• Loss of hpo results in elevated transcription of the cell cycle regulator cyclin E and the cell-death inhibitor diap1, leading to increased proliferation and reduced apoptosis [5].
• Ras upregulated the growth driver dMyc, and both Ras and dMyc increased levels of cyclin E posttranscriptionally [6].
• We propose that Ras primarily promotes growth and that growth is coupled to G1/S progression via cyclin E. Interestingly, upregulation of growth by Ras did not deregulate G2/M progression or a developmentally regulated cell cycle exit [6].

Biological context of CycE

• However, other components of the cell cycle seem to have a minor role in this process, suggesting a critical role for CycE in regulating cell fate in segment-specific neural lineages [7].
• Genetic studies have shown that cyclin E and dE2F are critical regulators of S-phase entry during Drosophila embryogenesis [8].
• We find that phosphorylation and degradation of Dup protein at G1/S requires cyclin E/CDK2 [9].
• In higher eukaryotes, cyclin E is thought to control the progression from G1 into S phase of the cell cycle by associating as a regulatory subunit with cdk2 [10].
• Analysis of a Drosophila cyclin E hypomorphic mutation suggests a novel role for cyclin E in cell proliferation control during eye imaginal disc development [11].

Anatomical context of CycE

• Archipelago regulates Cyclin E levels in Drosophila and is mutated in human cancer cell lines [12].
• Drosophila skpA, a component of SCF ubiquitin ligases, regulates centrosome duplication independently of cyclin E accumulation [13].
• CycE protein still cycles in cycE01672 germ-line cysts but at reduced levels, and it is found throughout a longer fraction of the cell cycle [14].
• CycE specifies neuronal fate within neuroblast lineages by acting upstream of glial factors (prospero and glial cell missing), whereby levels of CycE are controlled by homeotic genes, the master control genes regulating segment specific development [15].
• We suggest that Cyclin E also acts negatively to inhibit refiring of most origins within a cycle, and that specific factors at chorion origins allow them to escape this negative rereplication control [16].

Physical interactions of CycE

• These observations point to an important role for E2F-Rb complexes in the downregulation of cyclin E during the gap phase of endocycling cells in Drosophila development [17].
• Drosophila cyclin E interacts with components of the Brahma complex [18].
• dacapo encodes a CIP/KIP-type inhibitor of Cyclin E/Cdk2 complexes in Drosophila melanogaster [19].
• Roughex binds to Cyclin E and is a substrate for a Cyclin E-Cdk complex in vitro [20].

Regulatory relationships of CycE

• Expression of the cyclin-dependent kinase inhibitor Dacapo is regulated by cyclin E [21].
• During growth cone guidance, Prospero positively regulates cycE promoting cell proliferation [22].
• The Toll immune-regulated Drosophila protein Fondue is involved in hemolymph clotting and puparium formation [23].

Other interactions of CycE

• Dup is phosphorylated by cyclin-E/Cdk2, but this direct phosphorylation was not sufficient to explain the rapid destruction of Dup at G1-S [24].
• CycE, which is asymmetrically expressed after the first division of NB6-4t, functions upstream of pros and gcm to specify the neuronal sublineage [7].
• Because archipelago can also regulate Cyclin E levels and Notch activity, these results indicate how a single F box protein can be responsible for the degradation of key components of multiple pathways that control growth and cell cycle progression [25].
• Neither cyclin E nor E2F expression can phenocopy ana mutations, indicating that arrest caused by lack of Trol is different from Ana-mediated arrest [26].
• They specify the NB6-4a lineage by down-regulating levels of the G1 cyclin, DmCycE (CycE) [7].

Analytical, diagnostic and therapeutic context of CycE

• This study presents the first in vivo dissection of Cyclin E function [27].

References