The restriction point (R) separates two functionally different parts o
f G(1) in continuously cycling cells. G(1)-pm represents the postmitot
ic interval of G(1) that lasts from mitosis to R. G(1)-ps represents t
he pre S phase interval of G(1) that lasts from R to S. G(1)-pm is rem
arkably constant in length (its duration is about three hours) in the
different cell types studied so far. G(1)-ps, however, varies consider
ably, indicating that entry into S is not directly followed after pass
age through R. Progression through G(1)-pm requires continuous stimula
tion by mitogenic signals (e.g. growth factors) and a high rate of pro
tein synthesis. Interruption of the mitogenic signals or moderate inhi
bition of protein synthesis leads to a rapid exit from the cell cycle
to G(0) in normal (untransformed) cells. Upon restimulation with mitog
enic signals, the cell returns to the same point in G(1)-pm from which
it left the cell cycle. Thus the cell seems to have a memory for how
far it has advanced through G(1)-pm, suggesting that a continuous stru
ctural alteration, for example chromatin decondensation, takes place i
n G(1). The molecular background to transition from growth factor depe
ndence in G(1)-pm to growth factor independence in G(1)-ps (a switch w
hich represents commitment to a new cell cycle and passage through R)
is still not fully understood. Cyclin-dependent kinase (cdk)-mediated
hyperphosphorylation of the retinoblastoma protein (Rb), and concomita
nt liberation (and activation) of members of the E2F family of transcr
iption factors, are probably important aspects of R control in normal
cells. A key component here could be cdk2 activity which is controlled
by cyclin E. When cdk2 activity starts to increase rapidly in G(1), d
ue to activation of a positive feedback loop, it reaches a critical le
vel above which cdk inhibitors (CKls) such as p21 and p27 are outweigh
ed; the cell has then become independent of mitogenic and inhibitory s
ignals and is committed to a new cell cycle. However, other components
are probably also involved in R control. For instance, a 'cryptic' R
(a G(1)-pm-like state) can be induced even in tumour cells that do not
respond to growth factor starvation or protein synthesis inhibitors,
and are therefore probably defective in the cdk-Rb-E2F pathway. Possib
ly, a certain degree of chromatin decondensation has to take place aft
er mitosis in order to allow transcription of, for example, the cyclin
E gene or other critical E2F targets. Although the molecular basis fo
r restriction point control still remains unclear, we can expect rapid
progress in this important field over the next few years.