Regulation and function of capicua in mammals

Abstract

Capicua (CIC) is an evolutionarily conserved transcription factor. CIC contains a high-mobility group (HMG) box that recognizes specific DNA sequences to regulate the expression of various target genes. CIC was originally identified in Drosophila melanogaster as a transcriptional repressor that suppresses the receptor tyrosine kinase signaling pathway. This molecule controls normal organ growth and tissue patterning as well as embryogenesis in Drosophila. Recent studies have also demonstrated its extensive functions in mammals. For example, CIC regulates several developmental and physiological processes, including lung development, abdominal wall closure during embryogenesis, brain development and function, neural stem cell homeostasis, T cell differentiation, and enterohepatic circulation of bile acids. CIC is also associated with the progression of various types of cancer and neurodegeneration in spinocerebellar ataxia type-1, systemic autoimmunity, and liver injury. In this review, I provide a broad overview of our current understanding of the regulation and functions of CIC in mammals and discuss future research directions.

Capicua is a fast-acting transcriptional brake

“…[4][5][6] The highmobility group (HMG)-box transcription factor and repressor Capicua (Cic) regulates cell fate decisions during development and acts as a tumor suppressor in adult tissues. 2,7,8 From fruit flies to humans, Cic mediates inductive receptor tyrosine kinase (RTK) signaling. 1,[9][10][11] In the absence of RTK signals, Cic represses target genes, many of which are known oncogenes involved in cell proliferation.…”

Capicua Regulates Dendritic Morphogenesis Through Ets in Hippocampal Neurons in vitro

“…As Cic is an evolutionarily conserved transcription repressor (Lee, 2020), a possible mechanism for our findings is that Cic depresses specific genes that drive dendrite growth in neurons. Thus, Etv4 and Etv5 are candidate targets of interest.…”

“…Capicua (Cic), a member of the highly conserved high mobility group (HMG) box superfamily of transcription factors, promotes tumor progression and metastasis by directly controlling the transcription of effector target genes across human cancers ( Lee, 2020 ; Kim et al, 2021 ). Beyond its clear role in cancer, the function of Cic in hippocampal neurons has not been well studied.…”

Regulation of positive and negative selection and TCR signaling during thymic T cell development by capicua

“…CIC is expressed as two different isoforms: long (CIC-L) and short (CIC-S), which differ in their amino termini (Y. Lee, 2020). CIC recognizes specific octameric DNA sequences (5ʹ-T(G/C)AATG(A/G)(A/G)-3ʹ) within its target gene promoter regions and represses their expression (Kawamura-Saito et al, 2006;Shin & Hong, 2014;Weissmann et al, 2018).…”

“…Several genomic and transcriptomic analyses have identified CIC target genes, including ETV1, ETV4, ETV5, SPRY4, SPRED1, DUSP4, and DUSP6, in various types of cells (Fryer et al, 2011;Weissmann et al, 2018;Yang et al, 2017). Activation of the RTK/RAS/MAPK signaling pathway phosphorylates and inactivates CIC via dissociation from target gene promoters, cytoplasmic translocation, and/or proteasomal degradation (Jiménez et al, 2012;Keenan et al, 2020;Y. Lee, 2020).…”