The master regulator FUBP1: its emerging role in normal cell function and malignant development

Abstract

The human Far Upstream Element (FUSE) Binding Protein 1 (FUBP1) is a multifunctional DNA and RNA binding protein involved in diverse cellular processes. FUBP1 is a master regulator of transcription, translation, and RNA splicing. FUBP1 has been identified as a potent pro-proliferative and anti-apoptotic factor by modulation of complex networks. FUBP1 is also described either as an oncoprotein or a tumor suppressor. Especially, FUBP1 overexpression is observed in a growing number of cancer and leads to a deregulation of targets that includes the fine-tuned MYC oncogene.! Moreover, recent loss-of-function analyses of FUBP1 establish its essential functions in hematopoietic stem cell maintenance and survival. Therefore, FUBP1 appears as an emerging suspect in hematologic disorders in addition to solid tumors. The scope of the present review is to describe the advances in our understanding of the molecular basis of FUBP1 functions in normal cells and carcinogenesis. We also delineate the recent progresses in the understanding of the master role of FUBP1 in normal and pathological hematopoiesis. We conclude that FUBP1 is not only worth studying biologically but is also of clinical relevance through its pivotal role in regulating multiple cellular processes and its involvement in oncogenesis.!

Multiple Functions of Fubp1 in Cell Cycle Progression and Cell Survival

“…Previous reports showed that inactivating mutations of FUBP1 were detected in 15–20% of oligodendrogliomas [ 16 , 50 ], suggesting a tumor suppressive role of Fubp1. However, excessive expression of FUBP1 was documented in a variety of malignancies and FUBP1 abundance was often inversely correlated with overall survival [ 51 ], suggesting an oncogenic role of Fubp1. In the present study, we demonstrated the tumor-promoting function of Fubp1 by showing that Fubp1 transcriptionally activates cyclin A to promote cell cycle progression.…”

Small molecule recognition of disease-relevant RNA structures

“…108 Both cell-free and cell-based selective 2 0 hydroxyl acylation analyzed by primer extension (SHAPE) analysis showed that the addition of SMN-C2 altered the reactivity of some bases in TSL1, suggesting this compound induces conformational changes of this inhibitory loop. Further, proteomics analysis using a photo-cross-linking probe revealed enrichment of far upstream element binding protein 1 (FUBP1) 109 and far upstream element binding protein 2 (KHSRP). 110 Fluorescence polarization assays with SMN-C2 and recombinant FUBP1 induced higher polarization in the presence of ESE2.…”

Predicting the impact of sequence motifs on gene regulation using single-cell data

“…Comparison of TF expression levels and influence scores reveals that 39 of the 186 TFs associated with the nine motif families are strongly correlated with | r |>0.5 and a significant p-value ( Fig 3b ). For example, r <0 for FUBP1 with influence scores close to zero for the nephron progenitors but positive elsewhere, suggests that FUBP1 acts as a repressor in progenitors 32 . ETS family 2 shows a high positive correlation with ELF1 , and our analysis indicates that it is most important in immune cells, consistent with previous studies 33 .…”