CREB3 Antibody - #DF13792

Endoplasmic reticulum (ER)-bound sequence-specific transcription factor that directly binds DNA and activates transcription. Plays a role in the unfolded protein response (UPR), promoting cell survival versus ER stress-induced apoptotic cell death. Also involved in cell proliferation, migration and differentiation, tumor suppression and inflammatory gene expression. Acts as a positive regulator of LKN-1/CCL15-induced chemotaxis signaling of leukocyte cell migration. Associates with chromatin to the HERPUD1 promoter. Also induces transcriptional activation of chemokine receptors.

This is the transcriptionally active form that translocates to the nucleus and activates unfolded protein response (UPR) target genes during endoplasmic reticulum (ER) stress response. Binds the cAMP response element (CRE) (consensus: 5'-GTGACGT[AG][AG]-3') and C/EBP sequences present in many promoters to activate transcription of the genes. Binds to the unfolded protein response element (UPRE) consensus sequences sites. Binds DNA to the 5'-CCAC[GA]-3'half of ERSE II (5'-ATTGG-N-CCACG-3').

Functions as a negative transcriptional regulator in ligand-induced transcriptional activation of the glucocorticoid receptor NR3C1 by recruiting and activating histone deacetylases (HDAC1, HDAC2 and HDAC6). Also decreases the acetylation level of histone H4. Does not promote the chemotactic activity of leukocyte cells.

(Microbial infection) Plays a role in human immunodeficiency virus type 1 (HIV-1) virus protein expression.

(Microbial infection) Plays a role in herpes simplex virus-1 (HSV-1) latent infection and reactivation from latency. Represses the VP16-mediated transactivation of immediate early genes of the HSV-1 virus by sequestering host cell factor-1 HCFC1 in the ER membrane of sensory neurons, thereby preventing the initiation of the replicative cascade leading to latent infection.

(Microbial infection) May play a role as a cellular tumor suppressor that is targeted by the hepatitis C virus (HCV) core protein.

(Microbial infection) Activates transcription of genes required for reactivation of the latent HSV-1 virus. It's transcriptional activity is inhibited by CREBZF in a HCFC1-dependent manner, by the viral transactivator protein VP16. Binds DNA to the cAMP response element (CRE) (consensus: 5'-GTGACGT[AG][AG]-3') and C/EBP sequences present in many viral promoters.

(Microbial infection) It's transcriptional activity is inhibited by CREBZF in a HCFC1-dependent manner, by the viral transactivator HCV core protein.

First proteolytically cleaved by site-1 protease (S1P) that generates membrane-associated N-terminus and a luminal C-terminus forms. The membrane-associated N-terminus form is further proteolytically processed probably by the site-2 protease (S2P) through a regulated intramembrane proteolysis (RIP), releasing the transcriptional active processed cyclic AMP-responsive element-binding protein 3 form, which is transported to the nucleus. The proteolytic cleavage is strongly induced during dendritic cell (DC) maturation and inhibited by DCSTAMP. That form is rapidly degraded.

N-glycosylated.

Endoplasmic reticulum membrane>Single-pass type II membrane protein. Golgi apparatus.
Note: Colocalizes with HCFC1 in neuronal cell bodies of the trigeminal ganglia (PubMed:10623756). Colocalizes with DCSTAMP in the ER membrane of immature dendritic cell (DC) (PubMed:20546900). Colocalizes with CANX, CCR1, HCFC1 in the ER membrane (PubMed:10623756).

Nucleus. Cytoplasm.
Note: Predominantly in the nucleus (PubMed:19779205). Not associated with membranes (PubMed:19779205).

Nucleus.
Note: Upon RIP activation the transcriptional active processed cyclic AMP-responsive element-binding protein 3 form translocates into the nucleus. Detected in the nucleus upon dendritic cell maturation and RIP activation. Colocalizes with CREBRF in nuclear foci. Colocalizes with CREBZF in promyelocytic leukemia protein nuclear bodies (PML-NB).

Cytoplasm.
Note: (Microbial infection) Sequestered into the cytoplasm by the HCV core protein.

Ubiquitously expressed. Expressed in dendritic cells (DC). Weakly expressed in monocytes (at protein level).

Homodimer. Isoform 1 interacts with HCFC1; the interaction is required to stimulate CREB3 transcriptional activity. Isoform 1 interacts with CREBZF; the interaction occurs only in combination with HCFC1. Isoform 1 interacts (via central part and transmembrane region) with DCSTAMP (via C-terminus cytoplasmic domain). Isoform 1 interacts with OS9. Isoform 1 interacts (via leucine-zipper domain) with CREBRF (via leucine-zipper domain); the interaction occurs only after CREB3 activation and promotes CREB3 degradation. Isoform 1 interacts (via C-terminal domain) with CCR1.

(Microbial infection) Interacts with the HCV core protein; homodimerization is prevented by the HCV core protein. Isoform 1 interacts (via leucine-zipper and transmembrane domains) with HIV-1 TMgp41 (via cytoplasmic domain); the interaction reduces CREB3 stability. Processed cyclic AMP-responsive element-binding protein 3 interacts with HIV-1 Tat.

Belongs to the bZIP family. ATF subfamily.