Androgen receptor serine 81 mediates Pin1 interaction and activity

Hormone-dependent tumors are characterized by deregulated activity of specific steroid receptors, allowing aberrant expression of many genes involved in cancer initiation, progression and metastasis. In prostate cancer, the androgen receptor (AR) protein has pivotal functions, and over the years it has been the target of different drugs. AR is a nuclear receptor whose activity is regulated by a phosphorylation mechanism controlled by hormone and growth factors. Following phosphorylation, AR interacts with many cofactors that closely control its function. Among such cofactors, Pin1 is a peptidyl-prolyl isomerase that is involved in the control of protein phosphorylation and has a prognostic value in prostate cancer. In the present study, we demonstrate that ARSer81 is involved in the interaction with Pin1, and that this interaction is important for the transcriptional activity of AR. Since Pin1 expression positively correlates with tumor grade, our results suggest that Pin1 can participate in this process by modulating AR function.

[1]  A. Giordano,et al.  Dissecting Pin1 and phospho‐pRb regulation , 2013, Journal of cellular physiology.

[2]  Gillian H. Little,et al.  Runx2 controls a feed‐forward loop between androgen and prolactin‐induced protein (PIP) in stimulating T47D cell proliferation , 2012, Journal of cellular physiology.

[3]  Daniel Gioeli,et al.  Post-translational modification of the androgen receptor , 2012, Molecular and Cellular Endocrinology.

[4]  A. Klein-Szanto,et al.  Retinoblastoma tumor-suppressor protein phosphorylation and inactivation depend on direct interaction with Pin1 , 2012, Cell Death and Differentiation.

[5]  N. Guseva,et al.  Inhibition of p53 expression modifies the specificity of chromatin binding by the androgen receptor , 2012, Oncotarget.

[6]  S. Haslam,et al.  Regulation of Estrogen Receptor (cid:1) N-Terminus Conformation and Function by Peptidyl Prolyl Isomerase Pin1 , 2022 .

[7]  Q. Dou,et al.  Modulation of the tumor cell death pathway by androgen receptor in response to cytotoxic stimuli , 2011, Journal of cellular physiology.

[8]  D. Tindall,et al.  Androgen receptor rediscovered: the new biology and targeting the androgen receptor therapeutically. , 2011, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[9]  M. Napoli,et al.  Wiring the oncogenic circuitry: Pin1 unleashes mutant p53 , 2011, Oncotarget.

[10]  D. Tindall,et al.  Androgen receptor signaling in prostate cancer development and progression , 2011, Journal of carcinogenesis.

[11]  M. Menon,et al.  Calmodulin protects androgen receptor from calpain‐mediated breakdown in prostate cancer cells , 2011, Journal of cellular physiology.

[12]  W. Hahn,et al.  CDK9 regulates AR promoter selectivity and cell growth through serine 81 phosphorylation. , 2010, Molecular endocrinology.

[13]  A. Słupianek,et al.  The chromatin remodeling factor SRCAP modulates expression of prostate specific antigen and cellular proliferation in prostate cancer cells , 2010, Journal of cellular physiology.

[14]  K. Mahajan,et al.  Shepherding AKT and androgen receptor by Ack1 tyrosine kinase , 2010, Journal of cellular physiology.

[15]  G. Coetzee,et al.  Androgen receptor responsive enhancers are flanked by consistently-positioned H3-acetylated nucleosomes , 2010, Cell cycle.

[16]  D. Gioeli.  The promise of novel androgen receptor antagonists , 2010, Cell cycle.

[17]  P. Komarov,et al.  Small molecule screening reveals a transcription-independent pro-survival function of androgen receptor in castration-resistant prostate cancer , 2009, Cell cycle.

[18]  K. Morikawa,et al.  Proline cis/trans-Isomerase Pin1 Regulates Peroxisome Proliferator-activated Receptor γ Activity through the Direct Binding to the Activation Function-1 Domain* , 2009, The Journal of Biological Chemistry.

[19]  N. Weigel,et al.  Steroid receptor phosphorylation: Assigning function to site‐specific phosphorylation , 2009, BioFactors.

[20]  I. Raška,et al.  Inhibition of the peptidyl-prolyl-isomerase Pin1 enhances the responses of acute myeloid leukemia cells to retinoic acid via stabilization of RARalpha and PML-RARalpha. , 2009, Cancer research.

[21]  L. Butler,et al.  The contribution of different androgen receptor domains to receptor dimerization and signaling. , 2008, Molecular endocrinology.

[22]  K. Knudsen,et al.  Review Nuclear Receptor Signaling | The Open Access Journal of the Nuclear Receptor Signaling Atlas AR, the cell cycle, and prostate cancer , 2022 .

[23]  M. Conaway,et al.  Subcellular localization modulates activation function 1 domain phosphorylation in the androgen receptor. , 2007, Molecular endocrinology.

[24]  Thomas J. Smith,et al.  Initial hormonal management of androgen-sensitive metastatic, recurrent, or progressive prostate cancer: 2006 update of an American Society of Clinical Oncology practice guideline. , 2007, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[25]  G. Bubley,et al.  Androgen receptor phosphorylation and stabilization in prostate cancer by cyclin-dependent kinase 1 , 2006, Proceedings of the National Academy of Sciences.

[26]  B. E. Black,et al.  Stress kinase signaling regulates androgen receptor phosphorylation, transcription, and localization. , 2006, Molecular endocrinology.

[27]  Mark A. Rubin,et al.  Activation of β-Catenin Signaling in Prostate Cancer by Peptidyl-Prolyl Isomerase Pin1-Mediated Abrogation of the Androgen Receptor-β-Catenin Interaction , 2006, Molecular and Cellular Biology.

[28]  Akira Yamaguchi,et al.  Stable Suppression of Tumorigenicity by Pin1-Targeted RNA Interference in Prostate Cancer , 2005, Clinical Cancer Research.

[29]  T. Klimkait,et al.  The peptidyl–prolyl isomerase Pin1 regulates phospho-Ser77 retinoic acid receptor α stability , 2005 .

[30]  Mahadev Rao,et al.  The Androgen Receptor Acetylation Site Regulates cAMP and AKT but Not ERK-induced Activity* , 2004, Journal of Biological Chemistry.

[31]  J. Sowadski,et al.  Prevalent overexpression of prolyl isomerase Pin1 in human cancers. , 2004, The American journal of pathology.

[32]  T. Visakorpi,et al.  Molecular genetics of prostate cancer. , 2003, Annals of medicine.

[33]  Anna Frolov,et al.  The prolyl isomerase Pin1 is a novel prognostic marker in human prostate cancer. , 2003, Cancer research.

[34]  E. Gelmann,et al.  Molecular biology of the androgen receptor. , 2002, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[35]  S. Fuqua,et al.  Androgen Receptor Acetylation Governs trans Activation and MEKK1-Induced Apoptosis without Affecting In Vitro Sumoylation and trans-Repression Function , 2002, Molecular and Cellular Biology.

[36]  D. Feldman,et al.  The development of androgen-independent prostate cancer , 2001, Nature Reviews Cancer.

[37]  T. Hunter,et al.  Oncogenic kinase signalling , 2001, Nature.

[38]  J. Palvimo,et al.  Covalent modification of the androgen receptor by small ubiquitin-like modifier 1 (SUMO-1). , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[39]  E. Wilson,et al.  Identification of three proline-directed phosphorylation sites in the human androgen receptor. , 1995, Molecular endocrinology.

[40]  P. Riegman,et al.  The promoter of the prostate-specific antigen gene contains a functional androgen responsive element. , 1991, Molecular endocrinology.

[41]  J. Trapman,et al.  Hormone-dependent androgen receptor phosphorylation is accompanied by receptor transformation in human lymph node carcinoma of the prostate cells. , 1991, The Journal of biological chemistry.

[42]  J. Trapman,et al.  Androgen receptor heterogeneity and phosphorylation in human LNCaP cells. , 1990, Biochemical and biophysical research communications.

[43]  M. Beato.  Gene regulation by steroid hormones , 1989, Cell.

[44]  M. Rubin,et al.  Activation of beta-catenin signaling in prostate cancer by peptidyl-prolyl isomerase Pin1-mediated abrogation of the androgen receptor-beta-catenin interaction. , 2006, Molecular and cellular biology.

[45]  T. Klimkait,et al.  The peptidyl-prolyl isomerase Pin1 regulates phospho-Ser77 retinoic acid receptor alpha stability. , 2005, Biochemical and biophysical research communications.

[46]  A. Jemal,et al.  Cancer Statistics, 2005 , 2005, CA: a cancer journal for clinicians.

[47]  J. Shabanowitz,et al.  Androgen Receptor Phosphorylation REGULATION AND IDENTIFICATION OF THE PHOSPHORYLATION SITES* , 2002 .

[48]  N. Dubrawsky.  Cancer statistics , 1989, CA: a cancer journal for clinicians.