What is the role of cyclin E?

Cyclin E/cdk2 activity is regulated at multiple levels (by transcription, phosphorylation and inhibitor proteins) and appears to be involved in triggering initiation of DNA replication and in regulating genes important for proliferation and progression through S phase.

What is Cdk2?

Cyclin-dependent kinase 2 (CDK2) is a serine/threonine protein kinase, which has a role in the G1/S transition, the initiation of DNA synthesis and the regulation of the exit from S phase. In the G1/S phase, CDK4 and/or CDK6 in a complex with cyclin D initially phosphorylate the retinoblastoma (Rb) protein (12–15).

Where is cyclin E located?

Cyclin E overexpression was found in 50-60% of gastric adenomas and adenocarcinomas. In ~10% of colorectal carcinomas, cyclin E gene amplification is found, sometimes together with CDK2 gene amplification.

What type of regulator is cyclin E?

Cyclin E is a regulatory subunit of cyclin-dependent kinase (Cdk) 2 involved in many cellular processes including cell cycle progression, replication complex assembly, centrosome cycle, and epigenetic regulation.

What does Geminin protein do?

A nuclear protein present in most eukaryotes and highly conserved across species, numerous functions have been elucidated for geminin including roles in metazoan cell cycle, cellular proliferation, cell lineage commitment, and neural differentiation. One example of its function is the inhibition of Cdt1.

What happens in S phase?

S phase. In S phase, the cell synthesizes a complete copy of the DNA in its nucleus. It also duplicates a microtubule-organizing structure called the centrosome. The centrosomes help separate DNA during M phase.

Is CDK2 a gene?

CDK2 (Cyclin Dependent Kinase 2) is a Protein Coding gene. Diseases associated with CDK2 include Breast Cancer and Retinoblastoma. Among its related pathways are Cell cycle Cell cycle (generic schema) and Cell Cycle Checkpoints.

What is the function of cdc25?

CDC25C is a cyclin of the specific phosphatase family that activates the cyclin B1/CDK1 complex in cells for entering mitosis and regulates G2/M progression and plays an important role in checkpoint protein regulation in case of DNA damage, which can ensure accurate DNA information transmission to the daughter cells.

How is cyclin E destroyed?

Protein destruction is a major determinant of cyclin E periodicity, and cyclin E turnover is regulated by ubiquitin-mediated proteolysis. Cyclin E degradation is mediated through at least two distinct ubiquitin-proteasome pathways. The SCFFbw7 ubiquitin ligase targets Cdk2-bound, phosphorylated cyclin E.

What happens if DNA replication is inhibited?

These agents are bifunctional alkylating agents that can create crosslinks and/or bulky adducts that produce physical barriers which inhibit DNA synthesis. By stalling DNA synthesis, these lesions generate single-stranded DNA breaks (SSBs) and DSBs that can cause cell death if left unrepaired.

What activates Cdt1?

The human CDT1 gene has three putative E2F responsive elements in its promoter region, is activated by E2F with peak expression in late G1, and is inhibited by the Rb tumor suppressor [117].

How is the activity of cyclin E regulated?

This protein associates with and is regulated by the regulatory subunits of the complex including cyclin E or A. Cyclin E binds G1 phase Cdk2, which is required for the transition from G1 to S phase while binding with Cyclin A is required to progress through the S phase. Its activity is also regulated by phosphorylation.

Where did the name cyclin cell cycle come from?

In an interview for “The Life Scientific” (aired on 13/12/2011) hosted by Jim Al-Khalili, R. Timothy Hunt explained that the name “cyclin” was originally named after his hobby cycling. It was only after the naming did its importance in the cell cycle become apparent. As it was appropriate the name stuck. R.

How does cyclin E work on retinoblastoma cells?

Cyclin E/CDK2 phosphorylates retinoblastoma protein (Rb) to promote G1 progression. Hyper-phosphorylated Rb will no longer interact with E2F transcriptional factor, thus release it to promote expression of genes that drive cells to S phase through G1 phase. [1]

How does the cyclin family control the cell cycle?

Cyclin is a family of proteins that control the progression of cells through the cell cycle by activating cyclin-dependent kinase (CDK) enzymes.