TY - JOUR
T1 - Regulation of p27(Kip1) accumulation in murine B-lymphoma cells
T2 - Role of c-Myc and calcium
AU - Donjerković, Dubravka
AU - Zhang, Liying
AU - Scott, David W.
PY - 1999/10
Y1 - 1999/10
N2 - IgM cross-linking induces G1 arrest and apoptosis in murine B-lymphoma cells. It prevents pRb phosphorylation by decreasing cyclin-dependent kinase 2 activity via the up-regulation of cyclin kinase inhibitor p27(Kip1). Anti- IgM also causes an increase in cytosolic free calcium and a loss of c-Myc mRNA and protein. This down-regulation of c-Myc is prevented by CD40L, which rescues cells from anti-IgM-induced apoptosis. In this study, we addressed the mechanism(s) of anti-IgM-induced p27(Kip1) accumulation. We examined effects of early events in B-cell receptor-mediated signaling, c-Myc down- regulation, and an increase in free calcium on p27(Kip1). Down-regulation of c-myc alone had no effect on p27(Kip1); neither did an increase in free calcium alone. Together, these two events led to p27(Kip1) induction, growth arrest, and apoptosis. CD40L, the calcium chelator 1,2-bis(2- aminophenoxy)ethane-N,N,N',N'-tetraacetic acid-acetoxymethyl ester, and cyclosporin A all prevented anti-IgM-induced p27(Kip1) accumulation, suggesting that both the decrease in c-Myc expression and an increase in free calcium are necessary for p27(Kip1) up-regulation.
AB - IgM cross-linking induces G1 arrest and apoptosis in murine B-lymphoma cells. It prevents pRb phosphorylation by decreasing cyclin-dependent kinase 2 activity via the up-regulation of cyclin kinase inhibitor p27(Kip1). Anti- IgM also causes an increase in cytosolic free calcium and a loss of c-Myc mRNA and protein. This down-regulation of c-Myc is prevented by CD40L, which rescues cells from anti-IgM-induced apoptosis. In this study, we addressed the mechanism(s) of anti-IgM-induced p27(Kip1) accumulation. We examined effects of early events in B-cell receptor-mediated signaling, c-Myc down- regulation, and an increase in free calcium on p27(Kip1). Down-regulation of c-myc alone had no effect on p27(Kip1); neither did an increase in free calcium alone. Together, these two events led to p27(Kip1) induction, growth arrest, and apoptosis. CD40L, the calcium chelator 1,2-bis(2- aminophenoxy)ethane-N,N,N',N'-tetraacetic acid-acetoxymethyl ester, and cyclosporin A all prevented anti-IgM-induced p27(Kip1) accumulation, suggesting that both the decrease in c-Myc expression and an increase in free calcium are necessary for p27(Kip1) up-regulation.
UR - http://www.scopus.com/inward/record.url?scp=0032589803&partnerID=8YFLogxK
M3 - Article
C2 - 10547073
AN - SCOPUS:0032589803
SN - 1044-9523
VL - 10
SP - 695
EP - 704
JO - Cell Growth and Differentiation
JF - Cell Growth and Differentiation
IS - 10
ER -