C. Gieffers et al., Expression of the CDH1-associated form of the anaphase-promoting complex in postmitotic neurons, P NAS US, 96(20), 1999, pp. 11317-11322
Citations number
32
Categorie Soggetti
Multidisciplinary
Journal title
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
The anaphase-promoting complex/cyclosome (APC) is a tightly cell cycle-regu
lated ubiquitin-protein ligase that targets cyclin B and other destruction
box-containing proteins for proteolysis at the end of mitosis and in G1. Re
cent work has shown that activation of the APC in mitosis depends on CDC20,
whereas APC is maintained active in G1 via association with the CDC20-rela
ted protein CDH1. Here we show that the mitotic activator CDC20 is the only
component of the APC ubiquitination pathway whose expression is restricted
to proliferating cells, whereas the APC and CDH1 are also expressed in sev
eral mammalian tissues that predominantly contain differentiated cells, suc
h as adult brain. Immunocytochemical analyses of cultured rat hippocampal n
eurons and of mouse and human brain sections indicate that the APC and CDH1
are ubiquitously expressed in the nuclei of postmitotic terminally differe
ntiated neurons. The APC purified from brain contains all core subunits kno
wn from proliferating cells and is tightly associated with CDH1. Purified b
rain ApC(CDH1) has a high cyclin B ubiquitination activity that depends les
s on the destruction box than on the activity of mitotic ApC(CDC20). On the
basis of these results, we propose that the functions of ApC(CDH1) are not
restricted to controlling cell-cycle progression but may include the ubiqu
itination of yet unidentified substrates in differentiated cells.