Pip, a novel IRF family member, is a lymphoid-specific, PU.1-dependent transcriptional activator.
The immunoglobulin light-chain gene enhancers E kappa 3', E lambda 2-4, and E lambda 3-1 contain a conserved cell type-specific composite element essential for their activities. This element binds a B cell-specific heterodimeric protein complex that consists of the Ets family member PU.1 and a second factor (NF-EM5), whose participation in the formation of the complex is dependent on the presence of DNA-bound PU.1. In this report we describe the cloning and characterization of Pip (PU.1 interaction partner), a lymphoid-specific protein that is most likely NF-EM5. As expected, the Pip protein binds the composite element only in the presence of PU.1; furthermore, the formation of this ternary complex is critically dependent on phosphorylation of PU.1 at serine-148. The Pip gene is expressed specifically in lymphoid tissues in both B- and T-cell lines. When coexpressed in NIH-3T3 cells, Pip and PU.1 function as mutually dependent transcription activators of the composite element. The amino-terminal DNA-binding domain of Pip exhibits a high degree of homology to the DNA-binding domains of members of the interferon regulatory factor (IRF) family, which includes IRF-1, IRF-2, ICSBP, and ISGF3 gamma.
Eisenbeis
C F
CF
Department of Molecular Genetics and Cell Biology, University of Chicago, Illinois 60637, USA.
Singh
H
H
Storb
U
U
D000595:Amino Acid Sequence; D001483:Base Sequence; D002460:Cell Line; D003001:Cloning, Molecular; D004268:DNA-Binding Proteins / Q000235:genetics / Q000302:isolation & purification* / Q000378:metabolism*; D005786:Gene Expression Regulation; D006801:Humans; D050835:Interferon Regulatory Factors; D008214:Lymphocytes / Q000378:metabolism; D008969:Molecular Sequence Data; D015682:Retroviridae Proteins, Oncogenic; D016415:Sequence Alignment; D015534:Trans-Activators / Q000235:genetics / Q000302:isolation & purification* / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000302:isolation & purification* / Q000378:metabolism; D000099218:Interferon Regulatory Factor-4
D004268:DNA-Binding Proteins; D050835:Interferon Regulatory Factors; D015682:Retroviridae Proteins, Oncogenic; D015534:Trans-Activators; D014157:Transcription Factors; D000099218:Interferon Regulatory Factor-4; C062022:v-Spi-1 protein, Friend spleen focus-forming virus