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De androgeenreceptor is een transcriptiefactor

De androgeenreceptor is een transcriptiefactor. AR. Androgens. A. A. Δ Gene expression. Androgens. Testosterone Dihydrotestosterone. Androgens affect: - Embryologic development - Bone and muscle - Male puberty - Behaviour

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De androgeenreceptor is een transcriptiefactor

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  1. De androgeenreceptor is eentranscriptiefactor

  2. AR Androgens A A ΔGene expression

  3. Androgens Testosterone Dihydrotestosterone Androgens affect: - Embryologicdevelopment - Bone and muscle - Male puberty - Behaviour - Reproduction - Prostate & PrCa - Osteoporosis and frailty

  4. AR Androgens A A ΔGene expression

  5. Gene regulationbytestosterone • Testosteron binds the androgen receptor • The receptor binds DNA • The receptor activates gene expression • Therapies

  6. The receptor bindstestosterone AR: LBD AF2 DBD AF1 Gene activation DNA binding Ligand-binding

  7. Testosterone binds the receptor

  8. + ligand H9 H8 H1 H4 H5 H10 H7 H12 T H2 H11 H3 6 W Effect of testosterone binding no ligand H9 H8 H1 H4 H5 H10 S1 H7 LxxLL H3 S2 H2 6 H11 W H12

  9. Gene regulationbytestosterone • Testosteron activates the androgen receptor • The receptor binds DNA • The receptor activates gene expression • Therapies

  10. The DNA-binding domain of the AR AR: LBD AF2 DBD AF1

  11. How does testosterone affect gene expression? Ligand-binding AR: Gene activation DNA binding LBD AF2 DBD AF1

  12. Gene regulationbytestosterone • Testosteron binds the androgen receptor • The receptor binds DNA • The receptor activates gene expression

  13. Histon code and testosteron action AR: LBD AF2 DBD Tau-1 Tau-5 Chromatin-remodeling complex p160 TIF1β TFIIF CBP, P/CAF CARM1 Histon code recognition erasing RNApol II recruitment expression Histon code writing

  14. Testosteron effectson the histon code: a cartoon RNA polII -p160 AR AR -CRC AR AR -TFIIF -TIF1b

  15. The DBD and LBD communicate AR: Transactivation DNA binding Ligand-binding LBD AF2 DBD Tau-1 Tau-5 Cycling partners Cyclinghiston code

  16. Gene regulationbytestosterone • Testosteron binds the androgen receptor • The receptor binds DNA • The receptor activates gene expression • Prostate cancer

  17. New markers in prostate cancer 6,6 x 109 bp: A,C,G or T 107 Single nucleotide polymorphisms Gene fusions

  18. Gene fusions in PCa CTRL : Oncogenes 50% !

  19. Two SNPs in the TM-enhancer Chr 21: TMPRSS2 gene SNP1 A SNP2 T TM-ARE2 SNP1 SNP2

  20. Two SNPs in TM-ARE2 Chr 21 SNP1 A SNP2 T TM-ARE2 WT SNP1 SNP2

  21. Relevance of TM-ARE2 SNPs?

  22. Mol Endo Lab • AR stuctuur en functie • PrCaresistentietegenAR antagonisten • Nieuwe AR antagonisten • PrCagenomen en diagnostischemerkers • SNPs • Frailty: osteoporosis

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