which activates transcription through both consensus and variant cAMP response element (CRE) sites. MECT1 does not appear to modulate CREB1 DNA-binding activity but enhances the interaction of CREB1 with TAF4/TAFII-130. MECT1 translocates with MAML2 (MasterMind-Like Protein 2) to yield a fusion oncogene: t(11;19) (q21;p13). This translocation occurs in mucoepidermoid carcinomas, benign Warthin tumors and clear cell hidradenomas. The novel fusion product that results disrupts the Notch signaling pathway. The fusion protein consists of the N-terminus of MECT1 joined to the SLCterminus of MAML2. The reciprocal fusion protein consisting of the N-terminus of MAML2 joined to the SLCterminus of MECT1 has been detected in a small number of mucoepidermoid carcinomas. Multiple isoforms have been reported for the MECT1 protein.
Function:
Transcriptional coactivator for CREB1 which activates transcription through both consensus and variant cAMP response element (CRE) sites. Acts as a coactivator, in the SIK/TORC signaling pathway, being active when dephosphorylated and acts independently of CREB1 'Ser-133' phosphorylation. Enhances the interaction of CREB1 with TAF4. Regulates the expression of specific CREB-activated genes such as the steroidogenic gene, StAR. Potent coactivator of PGC1alpha and inducer of mitochondrial biogenesis in muscle cells. Also coactivator for TAX activation of the human T-cell leukemia virus type 1 (HTLSLV1) long terminal repeats (LTR). In the hippocampus, involved in late-phase long-term potentiation (L-LTP) maintenance at the Schaffer collateral-CA1 synapses. May be required for dendritic growth of developing cortical neurons (By similarity).
Subunit:
Binds, as a tetramer, through its N-terminal region, with the bZIP domain of CREB1. 'Arg-314' in the bZIP domain of CREB1 is essential for this interaction. Interaction, via its SLCterminal, with TAF4, enhances recruitment of TAF4 to CREB1. Binds HTLV1 Tax.
Subcellular Location:
Cytoplasm. Nucleus. Note=Cytoplasmic when phosphorylated by SIK or AMPK and when sequestered by 14-3-3 proteins (By similarity). Translocated to the nucleus on Ser-151 dephosphorylation, instigated by a number of factors including calcium ion and cAMP levels.
Tissue Specificity:
Highly expressed in adult and fetal brain. Located to specific regions such as the prefrontal cortex and cerebellum. Very low expression in other tissues such as heart, spleen, lung, skeletal muscle, salivary gland, ovary and kidney.
Post-translational modifications:
Phosphorylation/dephosphorylation states of Ser-151 are required for regulating transduction of CREB activity. TORCs are inactive when phosphorylated, and active when dephosphorylated at this site. This primary site of phosphorylation is mediated by SIKs (SIK1 and SIK2), is regulated by cAMP and calcium levels and is dependent on the phosphorylation of SIKs by LKB1 (By similarity). Phosphorylated upon DNA damage, probably by ATM or ATR
DISEASE:
Note=A chromosomal aberration involving CRTC1 is found in mucoepidermoid carcinomas, benign Warthin tumors and clear cell hidradenomas. Translocation t(11;19)(q21;p13) with MAML2. The fusion protein consists of the N-terminus of CRTC1 joined to the SLCterminus of MAML2. The reciprocal fusion protein consisting of the N-terminus of MAML2 joined to the SLCterminus of CRTC1 has been detected in a small number of mucoepidermoid carcinomas.
Similarity:
Belongs to the TORC family.
SWISS:
Q6UUV9
Gene ID:
23373
Database links:
Entrez Gene: 23373 Human
Entrez Gene: 382056 Mouse
Entrez Gene: 684527 Rat
Omim: 607536 Human
SwissProt: Q6UUV9 Human
SwissProt: Q68ED7 Mouse
SwissProt: Q157S1 Rat
Unigene: 371096 Human
Unigene: 428214 Human
Unigene: 227767 Mouse
Unigene: 208248 Rat
| Picture |
Paraformaldehyde-fixed, paraffin embedded (Rat brain); Antigen retrieval by boiling in sodium citrate buffer (pH6.0) for 15min; Block endogenous peroxidase by 3% hydrogen peroxide for 20 minutes; Blocking buffer (normal goat serum) at 37°C for 30min; Antibody incubation with (TORC1/CRTC1) Polyclonal Antibody, Unconjugated (SL3588R) at 1:400 overnight at 4°C, followed by operating according to SP Kit(Rabbit) (sp-0023) instructionsand DAB staining.
Blank control（black line）:SH-SY5Y.
Primary Antibody (green line): Rabbit Anti-CRTC1 antibody (SL3588R)
Dilution:2ug/Test;
Secondary Antibody（white blue line）: Goat anti-rabbit IgG-AF488
Dilution: 0.5ug/Test.
Isotype control（orange line）: Normal Rabbit IgG
Protocol
The cells were fixed with 4% PFA (10min at room temperature)and then permeabilized with 90% ice-cold methanol for 20 min at -20℃, The cells were then incubated in 5%BSA to block non-specific protein-protein interactions for 30 min at room temperature .Cells stained with Primary Antibody for 30 min at room temperature. The secondary antibody used for 40 min at room temperature. Acquisition of 20,000 events was performed.
Positive control: Hela cells
Concebtration: 5μg/10^6 cells
Incubation conditions: Avoid light , 30 minutes on the ice.
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