Identification of a Novel Family of Ankyrin Repeats Containing Cofactors for p160 Nuclear Receptor Coactivators

Abstract

Members of the p160 nuclear receptor coactivators interact with liganded nuclear receptors to enhance transcription of target genes. Here we identify a novel family of ankyrin repeats containing cofactors (ANCOs) that interact with the p160 coactivators. ANCO-1 binds to the conserved Per-Arnt-Sim (PAS) region of the p160 coactivators. It encodes a large nuclear protein with five ankyrin repeats, and parts of its sequences have been reported as nasopharyngeal carcinoma susceptibility protein and medulloblastoma antigen. Immunofluorescence staining reveals discrete nuclear foci of ANCO-1 that are distinct from known nuclear structures. Intriguingly, ANCO-1 also colocalizes and interacts with histone deacetylases. Transient reporter gene assay shows that ANCO-1 expression inhibits ligand-dependent transactivation by both steroid and nonsteroid nuclear receptors. Taken together, we have identified a novel family of ankyrin repeats containing cofactors that may recruit histone deacetylases to the p160 coactivators/nuclear receptor complex to inhibit ligand-dependent transactivation.

Identification of a Novel Gene, Anorexia, Regulating Feeding Activity via Insulin Signaling in Drosophila melanogaster

“…Ankyrin repeats are 33 amino acids long and involved in protein-protein interactions (32). Indeed, yeast two-hybrid screening using certain proteins with ankyrin repeats as bait has discovered several target proteins with an affinity for the ankyrin repeat domain (33). Based on these molecular characteristics, it is generally thought that many proteins with ankyrin repeats may play roles in integrating signals from multiple protein-protein interactions.…”

Identification of ANKRD11 as a p53 coactivator

“…LOH of human chromosome 16q occurs in at least half of all breast tumors (Miller et al, 2003) and cytogenetic studies have implicated this to be an early event in breast carcinogenesis (Gong et al, 2001). ANKRD11 (also termed ANCO1; official protein symbol ANR11) was also reported to interact with and suppress the function of the p160 coactivator family, including the oncogene AIB1 (amplified in breast cancer-1) (Zhang et al, 2004). AIB1 enhances ligand-dependent transactivation of steroid nuclear receptors, including estrogen receptor (ER), and is frequently amplified and overexpressed in breast and ovarian cancers (Anzick et al, 1997).…”

MECHANISMS IN ENDOCRINOLOGY: Novel genetic causes of short stature

“…The KBG syndrome is caused by a heterozygous mutation in ANKRD11 (176), encoding a member of a family of ankyrin repeat-containing cofactors that interacts with p160 nuclear receptor coactivators and inhibits ligand-dependent transcriptional activation (177).…”