Xm. Tang et al., CHANGES IN THE ACTIVITY OF CDK2 AND CDK5 ACCOMPANY DIFFERENTIATION OFRAT PRIMARY OLIGODENDROCYTES, Journal of cellular biochemistry, 68(1), 1998, pp. 128-137
Oligodendrocytes, the myelinating cells of the central nervous system,
are terminally differentiated cells that originate through asynchrono
us waves of proliferation and differentiation of precursors present at
birth. Withdrawal from cell cycle and onset of differentiation are ti
ghtly linked and depend on an intrinsic program modulated by the actio
n of growth factors. p27 plays a central and obligatory role in the in
itiation of oligodendrocyte differentiation and cessation of prolifera
tion. In this paper, we have characterized the role of modulation of c
dk2 and cdk5 kinase activity during the process of oligodendrocyte pre
cursor differentiation. As rat primary oligodendrocytes differentiate
in culture there is a fail in cdk2 activity and a rise in cdk5 activit
y as well as an increase in the cdk inhibitor, p27 protein. The declin
e in cdk2 activity is not accompanied by a drop in cdk2 protein level,
suggesting that it results from inhibition of cdk2 activation rather
than decreased protein expression. Taken together, these data suggest
that oligodendrocytes may withdraw from the cell cycle at G1-S transit
ion through inactivation of cdk2 activity, possibly initiated by incre
asing amount of p27, and that cdk5 may have a role until now unrecogni
zed in the differentiation of oligodendrocytes. (C) 1998 Wiley-Liss, I
nc.