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Structural highlights

Disease

[CREB1_HUMAN] Melanoma of soft part. 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=The gene represented in this entry may be involved in disease pathogenesis. 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. Note=A CREB1 mutation has been found in a patient with multiple congenital anomalies consisting of agenesis of the corpus callosum, cerebellar hypoplasia, severe neonatal respiratory distress refractory to surfactant, thymus hypoplasia, and thyroid follicular hypoplasia (PubMed:22267179).

Function

[CREB1_HUMAN] Phosphorylation-dependent transcription factor that stimulates transcription upon binding to the DNA cAMP response element (CRE), a sequence present in many viral and cellular promoters. Transcription activation is enhanced by the TORC coactivators which act independently of Ser-133 phosphorylation. Involved in different cellular processes including the synchronization of circadian rhythmicity and the differentiation of adipose cells. [CRTC2_MOUSE] 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 gluconeogenesis as a component of the LKB1/AMPK/TORC2 signaling pathway. Regulates the expression of specific genes such as the steroidogenic gene, StAR. Potent coactivator of PPARGC1A and inducer of mitochondrial biogenesis in muscle cells (By similarity).^{[1] [2]}

See Also

• CREB-binding protein 3D structures

References

1. ↑ Koo SH, Flechner L, Qi L, Zhang X, Screaton RA, Jeffries S, Hedrick S, Xu W, Boussouar F, Brindle P, Takemori H, Montminy M. The CREB coactivator TORC2 is a key regulator of fasting glucose metabolism. Nature. 2005 Oct 20;437(7062):1109-11. doi: 10.1038/nature03967. Epub 2005 Sep 7. PMID:16148943 doi:http://dx.doi.org/10.1038/nature03967
2. ↑ Shaw RJ, Lamia KA, Vasquez D, Koo SH, Bardeesy N, Depinho RA, Montminy M, Cantley LC. The kinase LKB1 mediates glucose homeostasis in liver and therapeutic effects of metformin. Science. 2005 Dec 9;310(5754):1642-6. Epub 2005 Nov 24. PMID:16308421 doi:http://dx.doi.org/1120781
3. ↑ Song Y, Zhai L, Valencia Swain J, Chen Y, Wang P, Chen L, Liu Y, Xiang S. Structural Insights into the CRTC2-CREB Complex Assembly on CRE. J Mol Biol. 2018 Jun 22;430(13):1926-1939. doi: 10.1016/j.jmb.2018.04.038. Epub, 2018 May 4. PMID:29733854 doi:http://dx.doi.org/10.1016/j.jmb.2018.04.038