Abstract
The cyclic-AMP response element-binding protein (CREB) is a nuclear transcription factor activated by phosphorylation at Ser133 by multiple serine/threonine (Ser/Thr) kinases. Upon phosphorylation, CREB binds the transcrip-tional co-activator' CBP (CREB-binding protein)' to initiate CREB-dependent gene transcription. CREB is a critical regulator of cell differentiation, proliferation and survival in the nervous system. Recent studies have shown that CREB is involved tumor initiation, progression and metastasis, supporting its role as a proto-oncogene. Overexpression and over-activation of CREB were observed in cancer tissues from patients with prostate cancer, breast cancer, non-small-cell lung cancer and acute leukemia while down-regulation of CREB in several distinct cancer cell lines resulted in inhibition of cell proliferation and induction of apoptosis, suggesting that CREB may be a promising target for cancer therapy. Although CREB, as a transcription factor, is a challenging target for small molecules, various small molecules have been discovered to inhibit CREB phosphorylation, CREB-DNA, or CREB-CBP interaction. These results suggest that CREB is a suitable transcription factor for drug targeting and therefore targeting CREB could represent a novel strategy for cancer therapy.
Original language | English (US) |
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Pages (from-to) | 384-391 |
Number of pages | 8 |
Journal | Current Cancer Drug Targets |
Volume | 10 |
Issue number | 4 |
DOIs | |
State | Published - 2010 |
Keywords
- CBP
- CREB
- Cancer
- Inhibitors
- KID
- KIX
- Naphthol AS-E
- Ro 31-8220
ASJC Scopus subject areas
- Oncology
- Pharmacology
- Drug Discovery
- Cancer Research