Tumor suppressors BTG1 and BTG2: Beyond growth control

• Published in: Journal of cellular physiology 2019-05, Vol.234 (5), p.5379-5389
• Main Authors: Yuniati, Laurensia, Scheijen, Blanca, Meer, Laurens T., Leeuwen, Frank N.
• Format: Article
• Language: English
• Subjects: Animals; antiproliferation; BTG1; BTG2; BTG2 protein; B‐cell malignancies; Cancer; Cell Cycle; Cell Differentiation; Cell division; Cell Proliferation; Deoxyribonucleic acid; Deregulation; DNA; DNA repair; Gene Expression Regulation, Neoplastic; Gene regulation; Genes; Genotoxicity; Hematopoiesis; Homeostasis; Humans; Immediate-Early Proteins - genetics; Immediate-Early Proteins - metabolism; Leukemia; Lymphocytes B; Lymphoma; Mini‐review; Mini‐reviews; Molecular modelling; mRNA stability; Neoplasm Proteins - genetics; Neoplasm Proteins - metabolism; Neoplasms - genetics; Neoplasms - metabolism; Neoplasms - pathology; Proteins; Ribonucleic acid; RNA; Signal Transduction; Solid tumors; Suppressors; Transcription; Transcription, Genetic; Translocation; tumor suppressor; Tumor Suppressor Proteins - genetics; Tumor Suppressor Proteins - metabolism; Tumors
• ISSN: 0021-9541; 1097-4652
• DOI: 10.1002/jcp.27407

Since the identification of B‐cell translocation gene 1 (BTG1) and BTG2 as antiproliferation genes more than two decades ago, their protein products have been implicated in a variety of cellular processes including cell division, DNA repair, transcriptional regulation and messenger RNA stability. In addition to affecting differentiation during development and in the adult, BTG proteins play an important role in maintaining homeostasis under conditions of cellular stress. Genomic profiling of B‐cell leukemia and lymphoma has put BTG1 and BTG2 in the spotlight, since both genes are frequently deleted or mutated in these malignancies, pointing towards a role as tumor suppressors. Moreover, in solid tumors, reduced expression of BTG1 or BTG2 is often correlated with malignant cell behavior and poor treatment outcome. Recent studies have uncovered novel roles for BTG1 and BTG2 in genotoxic and integrated stress responses, as well as during hematopoiesis. This review summarizes what is currently known about the roles of BTG1 and BTG2 in these and other cellular processes. In addition, we will highlight the molecular mechanisms and biological consequences of BTG1 and BTG2 deregulation during cancer progression and elaborate on the potential clinical implications of these findings. Members of the B‐cell translocation gene (BTG) protein family are important regulators of cellular differentiation and maintenance of homeostasis under conditions of cellular stress. This review describes these and other cellular functions, and highlights their emerging roles as potential tumor suppressors.