Identification of NAB1, a repressor of NGFI-A- and Krox20-mediated transcription.
NGFI-A (also called Egr1, Zif268, or Krox24) and the closely related proteins Krox20, NGFI-C, and Egr3 are zinc-finger transcription factors encoded by immediate-early genes which are induced by a wide variety of extracellular stimuli. NGFI-A has been implicated in cell proliferation, macrophage differentiation, synaptic activation, and long-term potentiation, whereas Krox20 is critical for proper hindbrain segmentation and peripheral nerve myelination. In previous work, a structure/function analysis of NGFI-A revealed a 34-aa inhibitory domain that was hypothesized to be the target of a cellular factor that represses NGFI-A transcriptional activity. Using the yeast two-hybrid system, we have isolated a cDNA clone which encodes a protein that interacts with this inhibitory domain and inhibits the ability of NGFI-A to activate transcription. This NGFI-A-binding protein, NAB1, is a 570-aa nuclear protein that bears no obvious sequence homology to known proteins. NAB1 also represses Krox20 activity, but it does not influence Egr3 or NGFI-G, thus providing a mechanism for the differential regulation of this family of immediate-early transcription factors.
Russo
M W
MW
Department of Pathology, Washington University School of Medicine, St. Louis, MO 63110, USA.
Sevetson
B R
BR
Milbrandt
J
J
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002451:Cell Compartmentation; D002467:Cell Nucleus / Q000737:chemistry; D018076:DNA, Complementary / Q000235:genetics; D004268:DNA-Binding Proteins / Q000378:metabolism*; D051766:Early Growth Response Protein 1; D051767:Early Growth Response Protein 2; D005786:Gene Expression Regulation; D015723:Gene Library; D017874:Immediate-Early Proteins; D051379:Mice; D008969:Molecular Sequence Data; D011485:Protein Binding; D012097:Repressor Proteins / Q000235:genetics* / Q000378:metabolism; D017422:Sequence Analysis, DNA; D017386:Sequence Homology, Amino Acid; D014157:Transcription Factors / Q000378:metabolism*; D014158:Transcription, Genetic
D018076:DNA, Complementary; D004268:DNA-Binding Proteins; D051766:Early Growth Response Protein 1; D051767:Early Growth Response Protein 2; C486109:Egr1 protein, mouse; C497327:Egr2 protein, mouse; D017874:Immediate-Early Proteins; C490624:Nab1 protein, mouse; D012097:Repressor Proteins; D014157:Transcription Factors