CIC (capicua transcriptional repressor)

Abstract

CIC is a tissue-specific transcriptional repressor that is highly conserved between metazoan organisms and is required for the normal development of multiple adult structures. CIC functions to transduce receptor tyrosine kinase (RTK) signalling into gene expression changes through a mechanism termed default repression, wherein CIC is bound to target gene promoters or enhancers and inhibits transcription in the absence of signal. This CIC-DNA interaction can be inhibited through activation of the RTK core signalling molecule mitogen-activated protein kinase (MAPK), which then allows for the transcription of CIC targets through this RTK-MAPK signalling axis. Components of RTK signalling are commonly dysregulated in cancers, possibly implying that CIC alterations observed in specific cancer types (e.g. oligodendroglioma and Ewing-like sarcomas) are a form of RTK signalling dysregulation that drives oncogenesis. CIC is also specifically expressed in cells of the developing central nervous system and its dysfunction is associated with the neurodegenerative disorder spinocerebellar ataxia type 1, implicating CIC in neuronal cell development and/or homeostasis. Other possible cellular and physiological roles for CIC include cell cycle control, ATP-citrate lyase phosphorylation, reactive oxygen species homeostasis, and bile acid homeostasis.