Negative and positive regulation by transcription factor cAMP response element-binding protein is modulated by phosphorylation.

Abstract

We have shown that the transcriptional activity of the protooncogenejun (c-jun)

Pivotal role of connective tissue growth factor in lung fibrosis: MAPK‐dependent transcriptional activation of type I collagen

“…However, growing evidence suggests mechanisms by which CREB can also act as a repressor (42,43). In one of these mechanisms, CREB, in its dephosphorylated form, competes with an activator (such as C/EBP␤) for binding to the CRE (43).…”

“…In one of these mechanisms, CREB, in its dephosphorylated form, competes with an activator (such as C/EBP␤) for binding to the CRE (43). Another mechanism involves weak binding of dephosphorylated CREB on AP-1 sites, which share highly homologous sequence motifs, and steric interference with the formation of c-Jun/c-Fos heterodimers (42). Either or both of these mechanisms are possible in the case of the CTGFinduced response on the Col1a2 promoter and are currently under more detailed investigation.…”

Unique Regulation of Immediate Early Gene and Tyrosine Hydroxylase Expression in the Odor-deprived Mouse Olfactory Bulb

“…Whereas gel supershift assays showed that CREB/CREM proteins are major components of the TH/CRE protein complexes, immunocytochemistry confirmed the binding data that CREB was unchanged in response to naris closure. Although CREB, thought to constitutively bind to the CRE motif, can be activated upon phosphorylation (12,14,15), pCREB was, if anything, variably increased in response to naris closure. Although Fos-B/Jun-D are present in the CRE-protein complexes, they represent only minor components.…”

“…Homodimers of Jun family members also bind with the AP-1 motif (11). The CRE motif is constitutively bound with the CRE-binding protein (CREB) and the CRE modulator protein (CREM) that are activated through phosphorylation (12)(13)(14)(15). The exact composition of the AP-1 and/or CRE DNA-protein complex remains controversial.…”

Transcriptional Control of Gene Expression by cAMP‐Response Element Binding Proteins

“…For example, the CAMP- In its unphosphorylated form, CREB may not just lack transcriptional transactivation activity but may even act as a repressor of transcription induced by other proteins. For example, it has been shown that a mutated form of CREB that cannot be phosphorylated by PKA is a negative transcriptional regulator of the c-jun protooncogene promoter (83). Also, in the somatostatinproducing pancreatic islet cell line RIN-1027-B2 ( 84), the existence of an inhibitor of PKA that prevents CREB phosphorylation renders CREB a repressor of somatostatin gene transcription induced by CIEBPP bound to the CRE (85).…”