Preferred Label : Cyclin E Degradation Pathway;
NCIt related terms : Cyclin E Destruction Pathway;
Alternative definition : BIOCARTA: Cyclins are proteins that associate with cyclin-dependent protein kinases
to regulate their activity and the progression of the cell cycle through specific
checkpoints. The cyclical increase and decrease in cyclin levels is a key to cell
cycle regulation. Disruption of cyclin action can lead to either cell cycle arrest,
or to uncontrolled cell proliferation. When cyclin E is abundant it interacts with
the cell cycle checkpoint kinase cdk2 to activate cdk2 and allow progression of the
cell cycle from G1 to S phase. One of the key targets of activated cdk2 complexed
with cyclin E is the tumor suppressor Rb. When dephosphorylated in G1, Rb complexes
with and blocks transcriptional activation by E2F transcription factors. When Rb is
phosphorylated by cdk2/Cyclin E, it dissociates from E2f, allowing E2F to activate
the transcription of genes required for S phase. One of the genes activated by E2F
is cyclin E itself, leading to a positive feedback cycle as cyclin E accumulates.
The decision by the cell to either remain in G1 or progress into S phase is the result
in part of the balance between cyclin E production and proteolytic degradation in
the proteasome. Cyclin E is targeted for destruction by the proteasome through ubiquitination
when associated with a complex of proteins called the SCF or F box complex. Proteins
included this complex include an F box protein that targets specific substrates such
as Cyclin E for degradation. In the case of cyclin E the F box protein Fbw7, also
called hCdc4, associates with phosphorylated free cyclin E to recruit it into the
SCF complex for degradation. SCFFbw7 is a ubiquitin ligase recruited into the complex
that specifically targets cyclin E. Cul3, skp1, and Rbx1 also are part of the complex
that degrades cyclin E. There may be redundancy for some components of the complex
since cul1 deletion also disrupts cyclin E degradation, and multiple F box proteins
may contribute to cyclin E degradation. The interaction of multiple different factors
in cyclin E accumulation integrates different signaling pathways with cell cycle regulation
and may play a role in the unregulated cell cycle progression of cancer. (This definition
may be outdated - see the DesignNote.);
NCIt note : The BIOCARTA Definition (ALT_DEFINITION) for this pathway concept was provided by
BioCarta. This property was not created by, nor is it maintained by the NCI Thesaurus
staff. Additionally, BioCarta is no longer updating its pathway data; thus, the BIOCARTA
Definition might be outdated or inaccurate. Please see the Terms and Conditions for
Use at http://www.biocarta.com/.;
Biocarta ID : h_fbw7Pathway;
Origin ID : C39078;
UMLS CUI : C1511580;
Semantic type(s)
- has_gene_product_element
- pathway_has_gene_element
