The Freud-1/CC2D1A family: Transcriptional regulators implicated in mental retardation

✍ Scribed by Anastasia Rogaeva; Kimberly Galaraga; Paul R. Albert

• Publisher: John Wiley and Sons
• Year: 2007
• Tongue: English
• Weight: 133 KB
• Volume: 85
• Category: Article
• ISSN: 0360-4012
• DOI: 10.1002/jnr.21277

✦ Synopsis

Abstract

The CC2D1A gene family consists of two homologous genes, Freud‐1/CC2D1A and Freud‐2/CC2D1B, that share conserved domains, including several DM14 domains that are specific to this protein family, a C‐terminal helix‐loop‐helix domain, and a C2 calcium‐dependent phospholipid binding domain. Although the function of Freud‐2 is unknown, Freud‐1 has been shown to function as a transcriptional repressor of the serotonin‐1A receptor gene that binds to a novel DNA element (FRE, 5′‐repressor element). The DNA binding and repressor activities of Freud‐1 are inhibited by calcium‐calmodulin‐dependent protein kinase. Recently, a deletion in the CC2D1A gene has been linked to nonsyndromic mental retardation. This deletion results in the truncation of the helix‐loop‐helix DNA binding and the C2 domains, crucial for Freud‐1 repressor activity, and hence is predicted to generate an inactive or weakly dominant negative protein. The possible mechanisms by which inactivation of Freud‐1 could lead to abnormal cortical development and cognitive impairment and the potential roles of Freud‐1 gene targets are discussed. © 2007 Wiley‐Liss, Inc.