CREB Signaling in Neural Stem/Progenitor Cells: Implications for a Role in Brain Tumors

Since its discovery in the PC12 rat pheochromocytoma cell line (Montminy & Bilezikjian 1987) the cAMP Response Element Binding (CREB) protein has been implicated in a variety of neuronal responses such as excitation, long-term memory formation, neural cell proliferation and opiate tolerance. Its importance is underscored by the attention this factor has attracted in the neuroscience community, as evidenced by the thousands of citations in the academic bibliographic databases. CREB is a transcription factor which potentially regulates the transcription of hundreds or even thousands of genes in neurons. A variety of protein kinases possess the capability of driving CREB phosphorylation and activation, placing CREB at a hub of multiple intraneuronal signalling cascades. The array of neuronal functions attributed to CREB has expanded recently, with studies showing that CREB has role in neural stem/progenitor cell growth, differentiation and survival. This data, together with complementary studies in tissues outside the CNS showing that CREB activation has oncogenic effects has led to the hypothesis that CREB has an important role in brain tumour biology. Therefore, CREB is a factor which sits within a molecular network potentially integrating signalling events regulating neural stem cells and neurogenesis, neural cancer cells and other cells within brain tumors.