A Novel Member of the RING Finger Family, KRIP-1, Associates with the KRAB-A Transcriptional Repressor Domain of Zinc Finger Proteins

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 93; no. 26; pp. 15299 - 15304
• Main Authors: Kim, Sung-Su, Chen, Yung-Ming, O'Leary, Eileen, Witzgall, Ralph, Vidal, Marc, Bonventre, Joseph V.
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences of the United States of America 24.12.1996; National Acad Sciences; National Academy of Sciences; The National Academy of Sciences of the USA
• Subjects: Amino Acid Sequence; Amino acids; Animals; Antibodies; Base Sequence; Biological Sciences; Complementary DNA; Conserved Sequence; COS Cells; Deoxyribonucleic acid; DNA; Embryo, Mammalian; Gene Library; Genetics; Kidney - metabolism; Mice; Molecular Sequence Data; Nuclear Proteins - biosynthesis; Nuclear Proteins - chemistry; Nuclear Proteins - metabolism; Plasmids; Proteins; Recombinant Fusion Proteins - metabolism; Repression; Repressor Proteins - metabolism; Transcription Factors - biosynthesis; Transcription Factors - chemistry; Transcription Factors - metabolism; Transfection; Tripartite Motif-Containing Protein 28; Yeast; Yeasts; Zinc; Zinc Fingers
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.93.26.15299

The Kruppel-associated box A (KRAB-A) domain is an evolutionarily conserved transcriptional repressor domain present in approximately one-third of zinc finger proteins of the Cys2-His2type. Using the yeast two-hybrid system, we report the isolation of a cDNA encoding a novel murine protein, KRAB-A interacting protein 1 (KRIP-1) that physically interacts with the KRAB-A region. KRIP-1 is a member of the RBCC subfamily of the RING finger, or Cys3HisCys4, family of zinc binding proteins whose other members are known to play important roles in differentiation, oncogenesis, and signal transduction. The KRIP-1 protein has high homology to TIF1, a putative modulator of ligand-dependent activation function of nuclear receptors. A 3.5-kb mRNA for KRIP-1 is ubiquitously expressed among all adult mouse tissues studied. When a GAL4-KRIP-1 fusion protein is expressed in COS cells with a chloramphenicol acetyltransferase reporter construct with five GAL4 binding sites, there is dose-dependent repression of transcription. Thus, KRIP-1 interacts with the KRAB-A region of C2H2zinc finger proteins and may mediate or modulate KRAB-A transcriptional repressor activity.