Zc. Qu et al., THE TRANSCRIPTIONAL COREPRESSOR NAB2 INHIBITS NGF-INDUCED DIFFERENTIATION OF PC12 CELLS, The Journal of cell biology, 142(4), 1998, pp. 1075-1082
The PC12 pheochromocytoma cell line responds to NGF by undergoing grow
th arrest and proceeding to differentiate toward a neuronal phenotype.
Among the early genetic events triggered by NGF in PC12 cells are the
rapid activation of the zinc finger transcription factor Egr1/NGFI-A,
and a slightly delayed induction of NAB2, a corepressor that inhibits
Egr1 transcriptional activity. We found that stably transfected PC12
cells expressing high levels of NAB2 do not differentiate, but rather
continue to proliferate in response to NGF. Inhibition of PC12 differe
ntiation by NAB2 overexpression was confirmed using two additional exp
erimental approaches, transient transfection, and adenoviral infection
. Early events in the NGF signaling cascade, such as activation of MAP
kinase and induction of immediate-early genes, were unaltered in the
NAB2-overexpressing PC12 cell lines. However, induction of delayed NGF
response genes such as TGF-beta 1 and MMP-3 was inhibited, Furthermor
e, NAB2 overexpression led to downregulation of p21(WAF1), a molecule
previously shown to play a pivotal role in the ability of PC12 cells t
o undergo growth arrest and commit to differentiation in response to N
GF, Cotransfection with p21(WAF1) restored the ability of NAB2-overexp
ressing PC12 cells to differentiate in response to NGF.