G2
S
M
G1
G0
Cyclin D-CDK4/6 regulates the G1/S checkpoint
Giacinti C, Giordano A. Oncogene 2006;
RB
RB
Gene
transcription
P
P
P
P
Inactive
Active tumour
suppressor
E2F
E2F
R
CDK4/6
Cyclin D
ER
Pl3K/Akt
MAPKs
Convergence of
mitogenic signaling
pathways on
cyclin D1 and CDK4/6
Binding of cyclin D1
to CDK4/6 induces
hyperphosphorylation
of Rb protein
Hyperphosphorylated
Rb loses its ability to
bind to the E2F family
of transcription factors
Continued activation of E2F
and transcription of several
genes required for the G1 to
S phase transition
Constant cell proliferation
leading to tumour
development
