What turns CREB on? And off? And why does it matter?
- PDF / 2,209,663 Bytes
- 19 Pages / 595.276 x 790.866 pts Page_size
- 81 Downloads / 191 Views
Cellular and Molecular Life Sciences
REVIEW
What turns CREB on? And off? And why does it matter? André Steven1 · Michael Friedrich1 · Paul Jank2 · Nadine Heimer1 · Jan Budczies3 · Carsten Denkert2 · Barbara Seliger1 Received: 14 November 2019 / Revised: 21 March 2020 / Accepted: 6 April 2020 © The Author(s) 2020
Abstract Altered expression and function of the transcription factor cyclic AMP response-binding protein (CREB) has been identified to play an important role in cancer and is associated with the overall survival and therapy response of tumor patients. This review focuses on the expression and activation of CREB under physiologic conditions and in tumors of distinct origin as well as the underlying mechanisms of CREB regulation by diverse stimuli and inhibitors. In addition, the clinical relevance of CREB is summarized, including its use as a prognostic and/or predictive marker as well as a therapeutic target. Keywords Transcription factor · CREB · Carcinogenesis · Prognosis · Clinical outcome Abbreviations ALL Acute lymphatic leukemia AML Acute myeloid leukemia ATF-1 Activating transcription factor 1 BC Breast cancer bZIP Basic leucine zipper CaMK Calcium-activated calmodulin kinase CBP CREB-binding protein CLL Chronic lymphatic leukemia CRE cAMP response element CREB cAMP response element-binding protein CREM cAMP response element modulator CRTC cAMP response transcriptional co-activator DNMT DNA methyltransferase ERK Extracellular signal-regulated kinase EWS Ewing’s sarcoma HR Hazard ratio Electronic supplementary material The online version of this article (https://doi.org/10.1007/s00018-020-03525-8) contains supplementary material, which is available to authorized users. * Barbara Seliger barbara.seliger@uk‑halle.de 1
Institute for Medical Immunology, Martin Luther University Halle-Wittenberg, Magdeburger Str. 2, 06112 Halle (Saale), Germany
2
Institute of Pathology, Philipps University Marburg, 35043 Marburg, Germany
3
Institute of Pathology, University Clinic Heidelberg, 69120 Heidelberg, Germany
KID Kinase-inducible domain KIX KID-interacting domain MAPK Mitogen-activated protein kinase MFS Metastasis-free survival miRNA microRNA OS Overall survival PI3K Phosphatidylinositol 3-kinase PK Protein kinase PP1 Protein phosphatase 1 PP2A Protein phosphatase 2A PTM Post-translational modification RBP RNA-binding protein RCC Renal cell cancer RFS Recurrence-free survival TCGA The Cancer Genome Atlas TF Transcription factor TME Tumor microenvironment TNBC Triple negative breast cancer UTR Untranslated region
Major characteristics of CREB Cyclic AMP (cAMP)-response element-binding protein 1 (CREB) is a 43 kDa stimulus-induced transcription factor (TF). It can bind to the cAMP response element (CRE) sequence TGACGTCA or the conserved half CRE TGACG and was first identified in the somatostatin gene promoter [1]. Genome-wide screening for CREB-binding sites suggested that more than 4000 genes might be controlled by
13
Vol.:(0123456789)
A. Stev
Data Loading...
