Tumor suppressors BTG1 and BTG2: Beyond growth control

Abstract

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.

Single-Cell Analysis of the Muscle Stem Cell Hierarchy Identifies Heterotypic Communication Signals Involved in Skeletal Muscle Regeneration

“…The role of Btg2 has not yet been previously described in myogenic cells. In hematopoietic and neural lineages, Btg2 promotes differentiation by inhibiting both Id3 and cyclin D1 to restrict cell cycle progression (Yuniati et al, 2019). Though we did not identify the mechanism of Btg2 regulation of myogenic differentiation, these data suggest Btg2 and Id3 are distinct transcriptional markers of quiescent MuSCs.…”

Deletion of Btg1 Induces Prmt1-Dependent Apoptosis and Increased Stemness in Shh-Type Medulloblastoma Cells Without Affecting Tumor Frequency

“…In this report, however, we observe that no significant change in tumor frequency of Ptch1 +/− mice occurs after deletion of Btg1. This is quite surprising given the increase of proliferation of cerebellar GCPs caused by the ablation of Btg1 in Patched1 wild-type background; moreover, Btg1 has been shown to act as oncosuppressor in MB cells which strongly inhibits the proliferation (12) and also in several types of tumors (14,29).…”

“…Genetic aberrations in Btg1 are common in B-cell malignancies (14), but this gene is also implicated in different types of solid tumors. In fact, deregulated expression of Btg1 is involved in gastric (15), kidney (16), liver (17), thyroid (18), nasopharyngeal (19), ovarian (20), breast (21,22), and non-small-cell lung cancers (23), and is frequently associated with disease severity.…”

Impaired adult hippocampal neurogenesis in Alzheimer’s disease is mediated by microRNA-132 deficiency and can be restored by microRNA-132 replacement

“…This approach revealed a novel miR-132-specific molecular signature consisting of DOCK1, EPHB3, BTG2, CAMK1 and RAC1 , all of which have reported roles in neuronal differentiation and function (Fortin et al, 2010; Goold and Nicoll, 2010; Pillat et al, 2016; Theus et al, 2010; Vadodaria et al, 2013; Yang et al, 2012). Dock1, Ephb3, Camk1 and Rac1 have additionally been implicated in AD (Aguilar et al, 2017; Becker et al, 2014; Overk and Masliah, 2014; Riascos et al, 2014), while all five proteins have been associated with the immune response in a variety of cells (D’Ambrosi et al, 2014; Goold and Nicoll, 2010; Guo et al, 2013; Naskar et al, 2014; Pillat et al, 2016; Theus et al, 2010; Yuniati et al, 2018). Interestingly, miR-132 knockdown also repressed the running-induced increase of Bdnf , a key neurotrophic factor contributing to the fitness of the niche and the neurogenic potential.…”