A New Kelch Domain Protein The Hclp-1 Functional Studies

Transcription regulation plays a crucial role in controlling the gene expression in response to metabolic requirements, developmental programs and a plethora of external stimuli. Transcription factors are the key component in the transcription machinery, while many transcription cofactors combine together with the transcription factors to orchestrate the whole transcription event. Nowadays, more and more transcription cofactors have been cloned and characterized in the field of functional genomic study.Our research work focuses on a group of kelch proteins which comprise more than 20 protein members. The kelch motif was discovered as a sixfold tandem element in the sequence of the Drosophila kelch 0RF1 protein. The repeated kelch motifs predict a conserved tertiary structure, a p-propeller. This module appears in many different polypeptide contexts and contains multiple potential protein-protein contact sites. Members of this growing superfamily are present throughout the cell and extracellularly and have diverse activities including transcription regulation.One member of the kelch superfamily-Host Cell Factor 1 (HCF-1) is a cellular transcriptional coactivator coordinating the assembly of enhancer complex through direct interactions with viral and cellular trans-activators such as VP16, Oct-1, LZIP and GA-binding protein. These interactions are mediated by the β-propeller domain comprising the first 380 residues of HCF-1 with six kelch repeats. Through the interaction and some unknown mechanisms, HCF involves the Herpes Simplex Virus infection and cell proliferation. Newly identified kelch proteins play important roles in cellular functions and disease development.Here we describe the identification and characterization of a novel HCF-like kelch repeat protein, designated HCLP-1 (AF113131). Full length HCLP-1 cDNA was isolated from human fetal brain cDNA library with library screening using the HCF-homological EST probe. HCLP-1 is comprised of 406...