The role of LANP and ataxin 1 in E4F-mediated transcriptional repression.
The leucine-rich acidic nuclear protein (LANP) belongs to the INHAT family of corepressors that inhibits histone acetyltransferases. The mechanism by which LANP restricts its repression to specific genes is unknown. Here, we report that LANP forms a complex with transcriptional repressor E4F and modulates its activity. As LANP interacts with ataxin 1--a protein mutated in the neurodegenerative disease spinocerebellar ataxia type 1 (SCA1)--we tested whether ataxin 1 can alter the E4F-LANP interaction. We show that ataxin 1 relieves the transcriptional repression induced by the LANP-E4F complex by competing with E4F for LANP. These results provide the first functional link, to our knowledge, between LANP and ataxin 1, and indicate a potential mechanism for the transcriptional aberrations observed in SCA1.
Cvetanovic
Marija
M
Davee Department of Neurology, Northwestern University Feinberg School of Medicine, Chicago, Illinois 60611, USA.
Rooney
Robert J
RJ
Garcia
Jesus J
JJ
Toporovskaya
Nataliya
N
Zoghbi
Huda Y
HY
Opal
Puneet
P
D000818:Animals; D000067696:Ataxin-1; D000067528:Ataxins; D002460:Cell Line; D045744:Cell Line, Tumor; D002522:Chlorocebus aethiops; D047369:Chromatin Immunoprecipitation; D017930:Genes, Reporter; D006367:HeLa Cells; D006801:Humans; D007150:Immunohistochemistry; D008156:Luciferases / Q000378:metabolism; D051379:Mice; D018832:Molecular Chaperones; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D009447:Neuroblastoma / Q000473:pathology; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism*; D011233:Precipitin Tests; D012097:Repressor Proteins / Q000378:metabolism*; D020754:Spinocerebellar Ataxias / Q000378:metabolism; D020798:Two-Hybrid System Techniques; D044767:Ubiquitin-Protein Ligases
C490336:ANP32E protein, human; C000593749:ATXN1 protein, human; D000067696:Ataxin-1; D000067528:Ataxins; C000593750:Atxn1 protein, mouse; D018832:Molecular Chaperones; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D010750:Phosphoproteins; D012097:Repressor Proteins; D008156:Luciferases; C513814:E4F1 protein, human; D044767:Ubiquitin-Protein Ligases