Hey1, a mediator of notch signaling, is an androgen receptor corepressor.
Hey1 is a member of the basic helix-loop-helix-Orange family of transcriptional repressors that mediate Notch signaling. Here we show that transcription from androgen-dependent target genes is inhibited by Hey1 and that expression of a constitutively active form of Notch is capable of repressing transactivation by the endogenous androgen receptor (AR). Our results indicate that Hey1 functions as a corepressor for AF1 in the AR, providing a mechanism for cross talk between Notch and androgen-signaling pathways. Hey1 colocalizes with AR in the epithelia of patients with benign prostatic hyperplasia, where it is found in both the cytoplasm and the nucleus. In marked contrast, we demonstrate that Hey1 is excluded from the nucleus in most human prostate cancers, raising the possibility that an abnormal Hey1 subcellular distribution may have a role in the aberrant hormonal responses observed in prostate cancer.
Belandia
Borja
B
Instituto de Investigaciones Biomédicas, Consejo Superior de Investigaciones Científicas and Universidad Autónoma de Madrid, 28029 Madrid, Spain. bbelandia@iib.uam.es
Powell
Sue M
SM
García-Pedrero
Juana M
JM
Walker
Marjorie M
MM
Bevan
Charlotte L
CL
Parker
Malcolm G
MG
D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins; D019556:COS Cells; D018797:Cell Cycle Proteins / Q000378:metabolism*; D002467:Cell Nucleus / Q000378:metabolism; D002522:Chlorocebus aethiops; D003593:Cytoplasm / Q000378:metabolism; D006367:HeLa Cells; D051548:Histone Acetyltransferases; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D056920:Nuclear Receptor Coactivator 1; D011470:Prostatic Hyperplasia / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000378:metabolism; D011944:Receptors, Androgen / Q000378:metabolism*; D051880:Receptors, Notch; D015398:Signal Transduction / Q000502:physiology*; D014157:Transcription Factors / Q000378:metabolism*; D015533:Transcriptional Activation; D014407:Tumor Cells, Cultured
D051792:Basic Helix-Loop-Helix Proteins; D018797:Cell Cycle Proteins; D051548:Histone Acetyltransferases; D008565:Membrane Proteins; D056920:Nuclear Receptor Coactivator 1; D011944:Receptors, Androgen; D051880:Receptors, Notch; D014157:Transcription Factors; C485631:HEY1 protein, human; C538859:NCOA1 protein, human; C538861:Ncoa1 protein, mouse