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PC12 cells regulate inducible cyclic AMP (cAMP) element repressor expression to differentially control cAMP response element‐dependent transcription in response to nerve growth factor and cAMP
Author(s) -
Chang Jay H.,
Vuppalanchi Deepika,
Van Niekerk Erna,
Trepel Jane B.,
Schanen N. Carolyn,
Twiss Jeffery L.
Publication year - 2006
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2006.04196.x
Subject(s) - repressor , response element , transcription factor , microbiology and biotechnology , cyclic gmp , serum response element , biology , bucladesine , cyclic amp response element binding protein , creb , chemistry , gene expression , endocrinology , serum response factor , gene , genetics , intracellular , promoter , nitric oxide
Both cyclic AMP (cAMP) and nerve growth factor (NGF) have been shown to cause rapid activation of cAMP response element‐binding protein (CREB) by phosphorylation of serine 133, but additional regulatory events contribute to CREB‐targeted gene expression. Here, we have used stable transfection with a simple cAMP response element (CRE)‐driven reporter to address the kinetics of CRE‐dependent transcription during neuronal differentiation of PC12 cells. In naive cells, dibutyryl cAMP (dbcAMP) generated a rapid increase in CRE‐driven luciferase activity by 5 h that returned to naive levels by 24 h. Luciferase induction after NGF treatment was delayed until 48 h when CRE‐driven luciferase expression became TrkA dependent. Blocking histone deacetylase (HDAC) activity accelerated NGF‐dependent CRE‐driven luciferase expression by at least 24 h and resulted in a sustained cAMP‐dependent expression of CRE‐driven luciferase beyond 24 h. Inhibition of protein synthesis before stimulation with NGF or dbcAMP indicated that both stimuli induce expression of a transcriptional repressor that delays NGF‐dependent and attenuates cAMP‐dependent CRE‐driven transcription. NGF caused a rapid but transient HDAC‐dependent increase in inducible cAMP element repressor (ICER) expression, but ICER expression was sustained with increased cAMP. Depletion of ICER from PC12 cells indicated that HDAC‐dependent ICER induction is responsible for the delay in CRE‐dependent transcription after NGF treatment.