Map Key
Generic Enzyme
Generic kinase
Protein kinase
Lipid kinase
Generic phosphatase
Protein phosphatase
Lipid phosphatase
Generic phospholipase
Generic protease
Metalloprotease
G-alpha
RAS - superfamily
G beta/gamma
Regulators (GDI, GAP, GEF)
Generic channel
Ligand-gated channel
Voltage-gated channel
Transporter
Normal process
Pathological process
Positive effect
Negative effect
Unspecified effect
Technical link
Disrupts in disease
Emerges in disease
Enhances in disease
Weakens in disease
Organsim specific interaction

Generic binding protein
Receptor ligand
Cell membrane glycoprotein
Transcription factor
DNA
RNA
Compound
Inorganic ion
Predicted metabolite or user's structure
Reaction
Generic receptor
GPCR
Receptors with enzyme activity
Mitochondria
EPR
Golgi
Nucleus
Lysosome
Peroxisome
Cytoplasm
Extracellular

Normal process
Pathological process
Binding
Cleavage
Covalent modifications
Phosphorylation
Dephosphorylation
Transformation
Transport
Catalysis
Transcription regulation
MicroRNA binding
Competition
Influence on expression
Unspecified interactions
Pharmacological effect
Toxic effect
Group relation
Complex subunit
Similarity reaction
A complex or a group
Organism specific object

Cell cycle Regulation of G1/S transition (part 2)


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Cell cycle Regulation of G1/S transition (part 2)

Regulation of G1/S transition (part 2)

The commencement of the cell cycle coincides with the production and the stabilizationof the Cyclin D. The D-type cyclins are essential for synchronization of the cellcycle machinery with extracellular signals. [1] Expression and stability ofCyclin D is monitored by growth factor receptors [2], [3] and focal adhesion-mediated [4], [5] signalingpathways.. Expression of Cyclin D may be activated through MAPK-cascade (viaSP1 [6], c-Fos, c-Jun [7] transfactors)and/or through AKT/ IKK/ NF-KB pathway [8]. Inaddition, AKT may inhibit GSK3 beta, thus preventing degradation ofCyclin D via the GSK3 -dependent pathway [9].

Cyclins D are positive-regulatory partners of cyclin-dependent kinase 4 (CDK4 ) and cyclin-dependent kinase 6 ( CDK6 ). Accumulating of CyclinD/ CDK complexes is activated by phosphorylation of CDK s by CAKcomplex [10].

CDK s inhibit retinoblastoma tumor suppressors (pRB)-family proteins ( Rbprotein, p107 and p130 ). pRB-family members are believed to functionthrough their effects on the transcription of genes regulated by the E2Ftranscription factors. CDK4 or CDK6 phosphorylate pRB-family members,thereby liberating E2Fs (for example, E2F1 or E2F4 ) [11]. These transcription factors associate with DP1 and together they induceexpression of Cyclin E, Cyclin A and some other proteins necessary for DNAreplication and the beginning of S phase. Cyclin E and Cyclin A arepositive-regulatory partners of cyclin-dependent kinase 2 ( CDK2 ). It isremarkable that both Cyclin D/ CDK4 (or CDK6 ) and CyclinE/CDK2 are necessary for induction of expression of Cyclin A [12], [13].

Activity of CDK s and Cyclines is inhibited by cell cycle kinaseinhibitors (for example, p27KIP [14] and other, see map). Duringtransition from G1 phase to S phase, p27KIP is exposed to ubiquitin-mediateddegradation by 26S proteasome [15], [16].