The transcription factor carbohydrate-response element-binding protein (ChREBP): A possible link between metabolic disease and cancer

• Published in: Biochimica et biophysica acta. Molecular basis of disease Vol. 1863; no. 2; pp. 474 - 485
• Main Author: Iizuka, Katsumi
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.02.2017
• Subjects: Animals; Basic Helix-Loop-Helix Leucine Zipper Transcription Factors - analysis; Basic Helix-Loop-Helix Leucine Zipper Transcription Factors - genetics; Basic Helix-Loop-Helix Leucine Zipper Transcription Factors - metabolism; ChREBP; Diabetes mellitus; Drug Discovery; Dyslipidemia; Gene Expression Regulation - drug effects; Glucose - genetics; Glucose - metabolism; Humans; Lipid Metabolism - drug effects; Metabolic Diseases - drug therapy; Metabolic Diseases - genetics; Metabolic Diseases - metabolism; Neoplasms - drug therapy; Neoplasms - genetics; Neoplasms - metabolism; Steatosis; Transcriptional Activation - drug effects; Tumorigenesis; ChREBP; Tumorigenesis; Diabetes mellitus; Dyslipidemia; Steatosis
• ISSN: 0925-4439; 1879-260X
• DOI: 10.1016/j.bbadis.2016.11.029

Carbohydrate-response element-binding protein (ChREBP) has been identified as a transcription factor that binds to carbohydrate response element in the promoter of pyruvate kinase, liver and red blood cells. ChREBP is activated by metabolites derived from glucose and suppressed by adenosine monophosphate (AMP), ketone bodies and cyclic cAMP. ChREBP regulates gene transcription related to glucose and lipid metabolism. Findings from knockout mice and human subjects suggest that ChREBP helps to induce hepatic steatosis, dyslipidemia, and glucose intolerance. Moreover, in tumor cells, ChREBP promotes aerobic glycolysis through p53 inhibition, resulting in tumor cell proliferation. Anti-diabetic and anti-lipidemic drugs such as atorvastatin, metformin, bile acid sequestrants, docosahexaenoic acid and eicosapentaenoic acid may affect ChREBP transactivity. Secretory proteins such as fibroblast growth factor 21 and ANGPTL8 (Betatrophin) may be promising candidates for biologic markers reflecting ChREBP transactivity. Thus, ChREBP is associated with metabolic diseases and cancers, and may be a link between them. •Carbohydrate-response element-binding protein (ChREBP) is a transcription factor.•ChREBP has roles in regulating glucose/lipid metabolism at the transcription level.•ChREBP contributes to fatty liver, glucose intolerance, dyslipidemia, and cancer.•Some drugs may modulate ChREBP activity, thereby improving hyperlipidemia/diabetes.•ChREBP may be a link between development of metabolic diseases and some cancers.