title: The androgen-induced protein AIbZIP facilitates proliferation of prostate cancer cells through downregulation of p21 expression.
abstract: Androgen-Induced bZIP (AIbZIP) is structurally a bZIP transmembrane transcription factor belonging to the CREB/ATF family. This molecule is highly expressed in androgen-sensitive prostate cancer cells and is transcriptionally upregulated by androgen treatment. Here, we investigated molecular mechanism of androgen-dependent expression of AIbZIP and its physiological function in prostate cancer cells. Our data showed that SAM pointed domain-containing ETS transcription factor (SPDEF), which is upregulated by androgen treatment, directly activates transcription of AIbZIP. Knockdown of AIbZIP caused a significant reduction in the proliferation of androgen-sensitive prostate cancer cells with robust expression of p21. Mechanistically, we demonstrated that AIbZIP interacts with old astrocyte specifically induced substance (OASIS), which is a CREB/ATF family transcription factor, and prevents OASIS from promoting transcription of its target gene p21. These findings showed that AIbZIP induced by the androgen receptor (AR) axis plays a crucial role in the proliferation of androgen-sensitive prostate cancer cells, and could be a novel target of therapy for prostate cancer.
authors.affiliation: Department of Biochemistry, Institute of Biomedical and Health Sciences, Hiroshima University, Hiroshima 734-8553, Japan.
authors.forename: Xiang
authors.initials: X
authors.lastname: Cui
authors.affiliation: Department of Biochemistry, Institute of Biomedical and Health Sciences, Hiroshima University, Hiroshima 734-8553, Japan.
authors.forename: Min
authors.initials: M
authors.lastname: Cui
authors.affiliation: Department of Biochemistry, Institute of Biomedical and Health Sciences, Hiroshima University, Hiroshima 734-8553, Japan.
authors.forename: Rie
authors.initials: R
authors.lastname: Asada
authors.affiliation: Department of Biochemistry, Institute of Biomedical and Health Sciences, Hiroshima University, Hiroshima 734-8553, Japan.
authors.forename: Soshi
authors.initials: S
authors.lastname: Kanemoto
authors.affiliation: Department of Biochemistry, Institute of Biomedical and Health Sciences, Hiroshima University, Hiroshima 734-8553, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Saito
authors.affiliation: Department of Biochemistry, Institute of Biomedical and Health Sciences, Hiroshima University, Hiroshima 734-8553, Japan.
authors.forename: Koji
authors.initials: K
authors.lastname: Matsuhisa
authors.affiliation: Department of Biochemistry, Institute of Biomedical and Health Sciences, Hiroshima University, Hiroshima 734-8553, Japan.
authors.forename: Masayuki
authors.initials: M
authors.lastname: Kaneko
authors.affiliation: Department of Biochemistry, Institute of Biomedical and Health Sciences, Hiroshima University, Hiroshima 734-8553, Japan.
authors.forename: Kazunori
authors.initials: K
authors.lastname: Imaizumi
mesh_terms: D000728:Androgens / Q000494:pharmacology; D050976:Basic-Leucine Zipper Transcription Factors / Q000502:physiology*; D001665:Binding Sites; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000235:genetics / Q000378:metabolism*; D015536:Down-Regulation; D015870:Gene Expression; D015972:Gene Expression Regulation, Neoplastic; D006056:Golgi Apparatus / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D008297:Male; D015741:Metribolone / Q000494:pharmacology; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009687:Nuclear Proteins / Q000502:physiology*; D011401:Promoter Regions, Genetic; D011471:Prostatic Neoplasms; D011485:Protein Binding; D059748:Proteolysis; D050783:Proto-Oncogene Proteins c-ets / Q000378:metabolism; D015398:Signal Transduction; D015533:Transcriptional Activation
chemical_list: D000728:Androgens; D050976:Basic-Leucine Zipper Transcription Factors; C493956:CDKN1A protein, human; C485618:CREB3L1 protein, human; C448322:CREB3L4 protein, human; D017362:Cyclic AMP Response Element-Binding Protein; D050759:Cyclin-Dependent Kinase Inhibitor p21; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D050783:Proto-Oncogene Proteins c-ets; C403974:SPDEF protein, human; D015741:Metribolone