Journal
CURRENT CANCER DRUG TARGETS
Volume 10, Issue 4, Pages 384-391Publisher
BENTHAM SCIENCE PUBL LTD
DOI: 10.2174/156800910791208535
Keywords
Cancer; CBP; CREB; inhibitors; KID; KIX; naphthol AS-E; Ro 31-8220
Categories
Funding
- Oregon Health & Science University
- Medical Research Foundation of Oregon
- Leukemia and Lymphoma Society of America, National Institutes of Health (NIH) [HL75826, HL83077]
- William Lawrence and Blanche Hughes Foundation
- St. Baldrick's Foundation
- NIH [HD034610-12/UCLA]
- Couples Against Leukemia/Ronald McDonald House Children's Cancer Research Fund [20091869]
- American Academy of Pediatrics Resident Research Award
- NATIONAL HEART, LUNG, AND BLOOD INSTITUTE [R01HL083077, R01HL075826] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES [R01GM087305] Funding Source: NIH RePORTER
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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 transcriptional 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 overactivation 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.
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