CREB1

CREB1 Full Name

cAMP responsive element binding protein 1

CREB1 Introduction

cAMP responsive element binding protein 1 (CREB1) is located in the nucleus and acts as a transcription factor. After phosphorylation by different receptor activated protein kinases such as protein kinase a (PKA), calmodulin dependent protein kinase (CaMK), mitogen activated protein kinase (MAPK), and other kinases at Ser133, it binds to the cAMP response element (CRE) of the target gene promoter. Once CREB is activated, CREB binding protein (CBP) is recruited and transcription begins. The activity of CREB in neurons is related to various intracellular processes, including proliferation, differentiation, survival, long-term synaptic enhancement, neurogenesis, and neuronal plasticity. Recent studies have shown that CREB is involved in the pathogenesis and treatment signaling pathways of certain mental disorders, including schizophrenia, making CREB an important focus of research.

Figure. Signaling cascade of CREB.(Source: Wang H, 2018)

The Molecular Structure of CREB
The CREB gene in mice and humans consists of 11 exons, which are selectively spliced to produce three subtypes named α, β, and Δ. These isoforms are expressed in most tissues and have the same function. Primary structural studies have shown that the full-length CREB sequence can be divided into four functional domains from the N-terminus to the C-terminus, namely (i) Q1 basic transcriptional active domain; (ii) Kinase inducible domain (KID); (iii) Q2 domain rich in glutamine for constitutive activation; The alkaline region/leucine zipper domain (bZIP) that forms homodimers and is responsible for binding to DNA. The Q1 domain is located at the N-terminus of CREB and interacts with TATA binding proteins to promote gene transcription. KID is located in the central region; The center of this region is Ser133, and phosphorylation of Ser133 by various protein kinases is necessary for activating CREB. The upstream protein kinases that activate CREB include PKA, Akt, protein kinase C (PKC), calcium/calmodulin dependent protein kinase II (CaMKII), p90 ribosomal S6 kinase (p90RSK), casein kinase I, and casein kinase II.

Figure. Molecular Structure of CREB.

The biological functions of CREB in the central nervous system
CREB is related to the regulation of various biological functions. The biological functions of the brain, such as the contribution of CREB to synaptic plasticity and neural development, have also been confirmed. Immunohistochemical analysis of CREB and ATF-1 showed that ATF-1 was expressed in the trophoblast and inner cell mass cells of mouse embryo E3.5. The expression of CREB can be detected at E3.5, and its expression increases in the later stages of epidermal progenitor cells and their derived cells. CREB deficient mice carry a mutation that can knock out all functional subtypes of the CREB gene. They are smaller than littermates and face survival issues due to breathing difficulties. Knockout of CREB and CREM in developing central nervous system neurons may lead to cell apoptosis, and postnatal ablation of these genes in adulthood may result in neuronal degeneration. Overall, these findings support the concept that CREB expression and transcriptional activity are regulated in both embryonic and mature brains, and are associated with neuronal survival and neurogenesis, which is a process related to the pathology of schizophrenia.

Alternate Names for CREB1

CREB1; cAMP responsive element binding protein 1; CREB; cyclic AMP-responsive element-binding protein 1; CREB-1; transactivator protein; active transcription factor CREB; cAMP-response element-binding protein-1; cAMP-responsive element-binding protein 1;

• 1.Wang H, Xu J, Lazarovici P, et al. cAMP response element-binding protein (CREB): a possible signaling molecule link in the pathophysiology of schizophrenia. Frontiers in molecular neuroscience. 2018, 11: 255.