ERK phosphorylation disrupts the intramolecular interaction of capicua to promote cytoplasmic translocation of capicua and tumor growth.

Activation of receptor tyrosine kinase signaling inactivates capicua (CIC), a transcriptional repressor that functions as a tumor suppressor, degradation and/or cytoplasmic translocation. Although CIC is known to be inactivated by phosphorylation, the mechanisms underlying the cytoplasmic translocation of CIC remain poorly understood. Therefore, we aimed to evaluate the roles of extracellular signal-regulated kinase (ERK), p90RSK, and c-SRC in the epidermal growth factor receptor (EGFR) activation-induced cytoplasmic translocation of CIC and further investigated the molecular basis for this process.

Postnatal regulation of B-1a cell development and survival by the CIC-PER2-BHLHE41 axis.

B-1 cell development mainly occurs via fetal and neonatal hematopoiesis and is suppressed in adult bone marrow hematopoiesis. However, little is known about the factors inhibiting B-1 cell development at the adult stage. We report that capicua (CIC) suppresses postnatal B-1a cell development and survival.

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

Central tolerance is achieved through positive and negative selection of thymocytes mediated by T cell receptor (TCR) signaling strength. Thus, dysregulation of the thymic selection process often leads to autoimmunity. Here, we show that Capicua (CIC), a transcriptional repressor that suppresses autoimmunity, controls the thymic selection process.

Deletion Timing of Alleles during Hematopoiesis Determines the Degree of Peripheral CD4 T Cell Activation and Proliferation.

Capicua (CIC) is a transcriptional repressor that regulates several developmental processes. CIC deficiency results in lymphoproliferative autoimmunity accompanied by expansion of CD44CD62L effector/memory and follicular Th cell populations. Deletion of alleles in hematopoietic stem cells (-mediated knockout of ) causes more severe autoimmunity than that caused by the knockout of in CD4CD8 double positive thymocytes (-mediated knockout of ).

Capicua deficiency induces autoimmunity and promotes follicular helper T cell differentiation via derepression of ETV5.

High-affinity antibody production through the germinal centre (GC) response is a pivotal process in adaptive immunity. Abnormal development of follicular helper T (T) cells can induce the GC response to self-antigens, subsequently leading to autoimmunity. Here we show the transcriptional repressor Capicua/CIC maintains peripheral immune tolerance by suppressing aberrant activation of adaptive immunity.

miR-93/miR-106b/miR-375-CIC-CRABP1: a novel regulatory axis in prostate cancer progression.

Capicua (CIC) has been implicated in pathogenesis of spinocerebellar ataxia type-1 (SCA1) neurodegenerative disease and some types of cancer; however, the role of CIC in prostate cancer remains unknown. Here we show that CIC suppresses prostate cancer progression. CIC expression was markedly decreased in human prostatic carcinoma.