CREB

CAMP responsive element binding protein 1, also known as CREB-1, plays multiple functions as a transcription factor in gene regulation. This protein is a CREB transcription factor that is a member of the leucine zipper family of DNA-binding proteins. CREB1 proteins are also known to be expressed in several spliced isoforms that act as transcriptional activators or repressors. The activator isoforms, possessing the functional domains for kinase induction and for interaction with other transcriptional regulators, act as transcriptional activators.The protein is phosphorylated by several protein kinases, and induces transcription of genes in response to hormonal stimulation of the cAMP pathway. CREB-1 has a complex influence on behavioural responses to drugs of abuse which varies depending on the brain region in which it is expressed. CREB-1 is important for serotonin (5-HT)-induced long-term facilitation (LTF) of the sensorimotor synapse in Aplysia.

CREB Related Areas

Signal Transduction>>Transcription Factor & Regulator>> CREB1

CREB Alternative Names

CREB, MGC9284 [Homo sapiens]

2310001E10Rik, 3526402H21Rik, AV083133, Creb, Creb-1 [Mus musculus]

Summaries for CREB

Entrez Gene summary for CREB:

CREB1 gene encodes a transcription factor that is a member of the leucine zipper family of DNA binding proteins. This CREB protein binds as a homodimer to the cAMP-responsive element, an octameric palindrome. The CREB protein is phosphorylated by several protein kinases, and induces transcription of genes in response to hormonal stimulation of the cAMP pathway. Alternate splicing of CREB1 gene results in two transcript variants encoding different isoforms. [provided by RefSeq, Jul 2008]

Wikipedia summary for CREB:

CREB (cAMP response element-binding) is a cellular transcription factor. It binds to certain DNA sequences called cAMP response elements (CRE), thereby increasing or decreasing the transcription of the downstream genes. CREB was first described in 1987 as a cAMP-responsive transcription factor regulating the somatostatin gene.

Genes whose transcription is regulated by CREB include: c-fos, the neurotrophin BDNF (Brain-derived neurotrophic factor), tyrosine hydroxylase, and many neuropeptides (such as somatostatin, enkephalin, VGF, and corticotropin-releasing hormone).

CREB is closely related in structure and function to CREM (cAMP response element modulator) and ATF-1 (activating transcription factor-1) proteins. CREB proteins are expressed in many animals, including humans. CREB is a transcription factor that has been show to be integral in the formation of spatial memory. In recent experiments it has been demonstrated that CREB may possess therapeutic potential for patients that have Alzheimer's Disease.

CREB has a well-documented role in neuronal plasticity and long-term memory formation in the brain.

Human CREB Protein General Information

 

• Protein names: Cyclic AMP-responsive element-binding protein 1 ,Short name=CREB-1
• Sequence length: 341 AA.
• Sequence similarities: Belongs to the bZIP family. Contains 1 bZIP domain. Contains 1 KID (kinase-inducible) domain.
• Post-translational modification: Stimulated by phosphorylation. Phosphorylation of both Ser-133 and Ser-142 in the SCN regulates the activity of CREB and participates in circadian rhythm generation. Phosphorylation of Ser-133 allows CREBBP binding . Phosphorylated upon DNA damage, probably by ATM or ATR. Phosphorylated upon calcium influx by CaMK4 and CaMK2 on Ser-133. CaMK4 is much more potent than CaMK2 in activating CREB. Phosphorylated by CaMK2 on Ser-142. Phosphorylation of Ser-142 blocks CREB-mediated transcription even when Ser-133 is phosphorylated. Phosphorylated by CaMK1 . Phosphorylation of Ser-271 by HIPK2 in response to genotoxic stress promotes CREB1 activity, facilitating the recruitment of the coactivator CBP. Phosphorylated at Ser-133 by RPS6KA3, RPS6KA4 and RPS6KA5 in response to mitogenic or stress stimuli.
• Subunit structure: Interacts with PPRC1. Binds DNA as a dimer. This dimer is stabilized by magnesium ions. Interacts, through the bZIP domain, with the coactivators TORC1/CRTC1, TORC2/CRTC2 and TORC3/CRTC3. When phosphorylated on Ser-133, binds CREBBP By similarity. Interacts (phosporylated form) with TOX3. Interacts with ARRB1. Binds to HIPK2. Interacts with SGK1.
• Subcellular location: Nucleus
• Involvement in disease: Defects in CREB1 may be a cause of angiomatoid fibrous histiocytoma (AFH) [MIM:612160]. A distinct variant of malignant fibrous histiocytoma that typically occurs in children and adolescents and is manifest by nodular subcutaneous growth. Characteristic microscopic features include lobulated sheets of histiocyte-like cells intimately associated with areas of hemorrhage and cystic pseudovascular spaces, as well as a striking cuffing of inflammatory cells, mimicking a lymph node metastasis. Note=A chromosomal aberration involving CREB1 is found in a patient with angiomatoid fibrous histiocytoma. Translocation t(2;22)(q33;q12) with CREB1 generates a EWSR1/CREB1 fusion gene that is most common genetic abnormality in this tumor type.

General information above from UniProt

Function for CREB Protein

UniProtKB:

CREB is a phosphorylation-dependent transcription factor that stimulates transcription upon binding to the DNA cAMP response element (CRE),CREB is a sequence present in many viral and cellular promoters. Transcription activation is enhanced by the TORC coactivators which act independently of Ser-133 phosphorylation. CREB is involved in different cellular processes including the synchronization of circadian rhythmicity and the differentiation of adipose cells.

Genatlas:

• CREB is an important regulator of cardiac myocyte function
• CREB roles in hippocampus-dependent learning
• CREB is crucial for the consolidation of long-term conditioned fear memories, but not for encoding, storage or retrieval of these memories
• CREB acts as a transcription regulator, with a role in survival of neurons (inhibition of neuronal suicide)
• CREB is involved in spermatogenesis
• CREB plays a role in neuronal protection
• CREB decreases the protein level of RCAN1
• role of CREB and CREM in stimulus-dependent transcription and neuronal homeostasis
• CREB has a context-dependent role in activity-regulated transcription and maintains neuronal cholesterol homeostasis
• CREB acts as a negative regulator of CCN1/CYR61 transcription
• CREB acts as a positive regulator of MMP2 expression and melanoma cell invasion (these effects can be explained, in part, by the CREB1-mediated inhibition of CCN1/CYR61 expression)
• photoreceptors degeneration leads to phosphorylation and increase expression of CREB1/ATF1 complex which is associated with a neuroprotective outcome in photoreceptors
• CREB is a central intracellular regulator in several signaling pathways and influences a variety of neural processes
• CREB is required for acquisition of ischemic tolerance, an endogenous neuroprotective mechanism whereby prior exposure to brief ischemia produces resilience to subsequent normally injurious ischemia
• CREB functions in concert with a family of latent cytoplasmic co-activators called cAMP-regulated transcriptional co-activators (CRTCs), which are activated through dephosphorylation
• CREB and CRTCs mediate the effects of fasting and feeding signals on the expression of metabolic programmes in insulin-sensitive tissues
• CREB is a novel protein target of PTEN phosphatase, which contributes to better understanding of PTEN function in the nucleus

Homology for human CREB

• ortholog to Creb1, Mus musculus
• ortholog to Creb1, rattus norvegicus
• ortholog to CREB1, Pan troglodytes
• ortholog to creb1, Danio rerio

Phenotype Information for CREB

• Gene/Locus: CREB1
• Phenotype: Histiocytoma, angiomatoid fibrous, somatic

Phenotype Information for CREB from OMIM (Online Mendelian Inheritance in Man)