Capicua transcriptional repressor (CIC)

Capicua transcriptional repressor (CIC) is a highly conserved transcription factor of the HMG-box family that functions as a key negative regulator of receptor tyrosine kinase (RTK)/RAS/MAPK signaling by binding specific DNA sites and repressing gene expression[1][3]. CIC was first discovered in *Drosophila*, where it coordinates embryonic tissue patterning and growth in response to RTK stimuli. In mammals, CIC plays crucial roles in development, tissue homeostasis, neural differentiation, T cell development, and tumor suppression. Mechanistically, CIC is inactivated by RAS/MAPK pathway activation through phosphorylation, cytoplasmic translocation, and degradation, thereby enabling expression of downstream target genes involved in cell proliferation and tissue growth. Loss-of-function mutations or oncogenic fusions (such as CIC-DUX4) are linked to various cancers (including oligodendroglioma and Ewing-like sarcoma), while interaction with mutant ataxin-1 is associated with spinocerebellar ataxia type-1. CIC has emerged as a determinant of therapeutic sensitivity to MAPK and EGFR inhibitors, highlighting its significance as a potential biomarker and an indirect therapeutic target[1][2][3].

Other names

CapicuaCICCapicua homologCapicua (HMG-box transcription factor)Capicua (protein)

No drugs are known to directly target CIC; however, CIC status is linked to responsiveness to EGFR inhibitors and MAPK pathway inhibitors (modulates sensitivity as a downstream effector)[1].