NDLI: Fkbp52 Regulates Androgen Receptor Transactivation Activity and Male Urethra Morphogenesis*

Content Provider	PubMed Central
Author	Chen, Hanying Yong, Weidong Hinds, Terry D. Yang, Zuocheng Zhou, Yuhong Sanchez, Edwin R. Shou, Weinian
Abstract	Hypospadias is a common birth defect in humans, yet its etiology and pattern of onset are largely unknown. Recent studies have shown that male mice with targeted ablation of FK506-binding protein-52 (Fkbp52) develop hypospadias, most likely due to actions of Fkbp52 as a molecular co-chaperone of the androgen receptor (AR). Here, we further dissect the developmental and molecular mechanisms that underlie hypospadias in Fkbp52-deficient mice. Scanning electron microscopy revealed a defect in the elevation of prepucial swelling that led to the onset of the ventral penile cleft. Interestingly, expression of Fkbp52 was highest in the ventral aspect of the developing penis that undergoes fusion of the urethral epithelium. Although in situ hybridization and immunohistochemical analyses suggested that Fkbp52 mutants had a normal urethral epithelium signaling center and epithelial differentiation, a reduced apoptotic cell index at ventral epithelial cells at the site of fusion and a defect of genital mesenchymal cell migration were observed. Supplementation of gestating females with excess testosterone partially rescued the hypospadic phenotype in Fkbp52 mutant males, showing that loss of Fkbp52 desensitizes AR to hormonal activation. Direct measurement of AR activity was performed in mouse embryonic fibroblast cells treated with dihydrotestosterone or synthetic agonist R1881. Reduced AR activity at genes controlling sexual dimorphism and cell growth was found in Fkbp52-deficient mouse embryonic fibroblast cells. However, chromatin immunoprecipitation analysis revealed normal occupancy of AR at gene promoters, suggesting that Fkbp52 exerts downstream effects on the transactivation function of AR. Taken together, our data show Fkbp52 to be an important molecular regulator in the androgen-mediated pathway of urethra morphogenesis.
Related Links	http://dx.doi.org/10.1074/jbc.M110.156091
Ending Page	27784
Page Count	9
Starting Page	27776
File Format	PDF
ISSN	1083351X
e-ISSN	1083351X
Journal	The Journal of Biological Chemistry
Issue Number	36
Volume Number	285
Language	English
Publisher	American Society for Biochemistry and Molecular Biology
Publisher Date	2010-09-03
Access Restriction	Open
Rights Holder	American Society for Biochemistry and Molecular Biology
Subject Keyword	Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Cell Biology Biochemistry Molecular Biology

Sl.	Authority	Responsibilities	Communication Details
1	Ministry of Education (GoI), Department of Higher Education	Sanctioning Authority	https://www.education.gov.in/ict-initiatives
2	Indian Institute of Technology Kharagpur	Host Institute of the Project: The host institute of the project is responsible for providing infrastructure support and hosting the project	https://www.iitkgp.ac.in
3	National Digital Library of India Office, Indian Institute of Technology Kharagpur	The administrative and infrastructural headquarters of the project	Dr. B. Sutradhar bsutra@ndl.gov.in
4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
5	Website/Portal (Helpdesk)	Queries regarding NDLI and its services	support@ndl.gov.in
6	Contents and Copyright Issues	Queries related to content curation and copyright issues	content@ndl.gov.in
7	National Digital Library of India Club (NDLI Club)	Queries related to NDLI Club formation, support, user awareness program, seminar/symposium, collaboration, social media, promotion, and outreach	clubsupport@ndl.gov.in
8	Digital Preservation Centre (DPC)	Assistance with digitizing and archiving copyright-free printed books	dpc@ndl.gov.in
9	IDR Setup or Support	Queries related to establishment and support of Institutional Digital Repository (IDR) and IDR workshops	idr@ndl.gov.in

Fkbp52 Regulates Androgen Receptor Transactivation Activity and Male Urethra Morphogenesis

Androgen Receptor Splice Variants are Resistant to Inhibitors of Hsp90 and FKBP52, which alter Androgen Receptor Activity and Expression

Essential Role for Co-Chaperone FKBP52 but not FKBP51 in Androgen Receptor-Mediated Signaling and Physiology

The Presence of Androgen Receptor Elements Regulates ZEB1 Expression in the Absence of Androgen Receptor

Primate-specific Melanoma Antigen-A11 Regulates Isoform-specific Human Progesterone Receptor-B Transactivation*

Hydrogen Sulfide Represses Androgen Receptor Transactivation by Targeting at the Second Zinc Finger Module*

Androgen Receptor Exon 1 Mutation Causes Androgen Insensitivity by Creating Phosphorylation Site and Inhibiting Melanoma Antigen-A11 Activation of NH2- and Carboxyl-terminal Interaction-dependent Transactivation*

ARA67/PAT1 Functions as a Repressor To Suppress Androgen Receptor Transactivation

ARA67/PAT1 Functions as a Repressor To Suppress Androgen Receptor Transactivation

Fkbp52 Regulates Androgen Receptor Transactivation Activity and Male Urethra Morphogenesis*

Similar Documents

Fkbp52 Regulates Androgen Receptor Transactivation Activity and Male Urethra Morphogenesis

Androgen Receptor Splice Variants are Resistant to Inhibitors of Hsp90 and FKBP52, which alter Androgen Receptor Activity and Expression

Essential Role for Co-Chaperone FKBP52 but not FKBP51 in Androgen Receptor-Mediated Signaling and Physiology

The Presence of Androgen Receptor Elements Regulates ZEB1 Expression in the Absence of Androgen Receptor

Primate-specific Melanoma Antigen-A11 Regulates Isoform-specific Human Progesterone Receptor-B Transactivation*

Hydrogen Sulfide Represses Androgen Receptor Transactivation by Targeting at the Second Zinc Finger Module*

Androgen Receptor Exon 1 Mutation Causes Androgen Insensitivity by Creating Phosphorylation Site and Inhibiting Melanoma Antigen-A11 Activation of NH2- and Carboxyl-terminal Interaction-dependent Transactivation*

ARA67/PAT1 Functions as a Repressor To Suppress Androgen Receptor Transactivation

ARA67/PAT1 Functions as a Repressor To Suppress Androgen Receptor Transactivation

Fkbp52 Regulates Androgen Receptor Transactivation Activity and Male Urethra Morphogenesis*