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Typus
Verschleierung
Bearbeiter
Hindemith
Gesichtet
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Untersuchte Arbeit:
Seite: 23, Zeilen: 6-19
Quelle: Ward and Weigel 2009
Seite(n): 6 (author manuscript), Zeilen: 34 ff.
Like PR, the majority of identified phosphorylation sites for AR are located in the N-terminal domain. Although many of the NTD sites have been tested in vivo, assigning function to them has been difficult. Studies of transcriptional activation by AR on several androgen response elements containing promoters carried out in various cell lines has provided little information on the function of NTD sitespecific phosphorylation, Many phosphorylation mutants exhibited no aberrant activation characteristics when compared with wild type.(35,36,37,38). However, greater differences in activity can be detected when specific signaling pathways are activated or inhibited. For example, overexpression of cyclin D3/CDK11p58 inhibits AR activity by phosphorylating Ser308A mutant partially elevates hormone dependent activity and prevents cyclin D3/ CDK11p58- mediated repression of AR transcriptional activity (39).

35) Zhou, Z. X., Kemppainen, J. A., and Wilson, E. M. (1995) Identification of three proline-directed phosphorylation sites in the human androgen receptor. Mol. Endocrinol. 9, 605–615.

36) Zhu, Z., Becklin, R. R., Desiderio, D. M., and Dalton, J. T. (2001) Identification of a novel phosphorylation site in human androgen receptor by mass spectrometry. Biochem. Biophys. Res. Commun. 284, 836–844.

37) Yang, C. S., Vitto, M. J., Busby, S. A., Garcia, B. A., Kesler, C. T., Gioeli, D., Shabanowitz, J., Hunt, D. F., Rundell, K., Brautigan, D. L., and Paschal, B. M. (2005) Simian virus 40 small t antigen mediates conformation- dependent transfer of protein phosphatase 2A onto the androgen receptor. Mol. Cell Biol. 25, 1298–1308.

38) Gioeli, D., Ficarro, S. B., Kwiek, J. J., Aaronson, D., Hancock, M., Catling, A. D., White, F. M., Christian, R. E., Settlage, R. E., Shabanowitz, J., Hunt, D. F., and Weber, M. J. (2002) Androgen receptor phosphorylation. Regulation and identification of the phosphorylation sites. J. Biol. Chem. 277, 29304–29314.].

39) Zong, H., Chi, Y., Wang, Y., Yang, Y., Zhang, L., Chen, H., Jiang, J., Li, Z., Hong, Y., Wang, H., Yun, X., and Gu, J. (2007) Cyclin D3/CDK11p58 complex is involved in the repression of androgen receptor. Mol. Cell Biol. 27, 7125–7142.

Like PR, the majority of identified phosphorylation sites for AR are located in the N-terminal domain (Figure 2). Although many of the NTD sites have been verified in vivo, assigning function to them has been difficult. Studies of transcriptional activation by AR of several androgen response elements containing promoters carried out in various cell lines has provided little information as to the function of NTD site-specific phosphorylation as many phosphorylation mutants have exhibited no aberrant activation characteristics when compared to wild type (56-60). However, greater differences in activity can be detected when specific signaling pathways are activated or inhibited. For example, overexpression of cyclin D3/CDK11p58 inhibits AR activity. The kinase phosphorylates Ser308; substitution of an alanine elevates hormone dependent activity modestly and prevents cyclin D3/ CDK11p58 mediated repression of AR transcriptional activity (61).

56. Zhou ZX, Kemppainen JA, Wilson EM. Identification of three proline-directed phosphorylation sites in the human androgen receptor. Mol Endocrinol. 1995; 9:605–615. [PubMed: 7565807]

57. Zhu Z, Becklin RR, Desiderio DM, Dalton JT. Identification of a novel phosphorylation site in human androgen receptor by mass spectrometry. Biochem Biophys Res Commun. 2001; 284:836– 844. [PubMed: 11396978]

58. Yang CS, Vitto MJ, Busby SA, Garcia BA, Kesler CT, Gioeli D, Shabanowitz J, Hunt DF, Rundell K, Brautigan DL, Paschal BM. Simian virus 40 small t antigen mediates conformation dependent transfer of protein phosphatase 2A onto the androgen receptor. Mol Cell Biol. 2005; 25:1298–1308. [PubMed: 15684382]

59. Gioeli D, Ficarro SB, Kwiek JJ, Aaronson D, Hancock M, Catling AD, White FM, Christian RE, Settlage RE, Shabanowitz J, Hunt DF, Weber MJ. Androgen receptor phosphorylation. Regulation and identification of the phosphorylation sites. J Biol Chem. 2002; 277:29304–29314. [PubMed: 12015328]

60. Chen S, Xu Y, Yuan X, Bubley GJ, Balk SP. Androgen receptor phosphorylation and stabilization in prostate cancer by cyclin-dependent kinase 1. Proc Natl Acad Sci U S A. 2006; 103:15969–15974. [PubMed: 17043241]

61. Zong H, Chi Y, Wang Y, Yang Y, Zhang L, Chen H, Jiang J, Li Z, Hong Y, Wang H, Yun X, Gu J. Cyclin D3/CDK11p58 complex is involved in the repression of androgen receptor. Mol Cell Biol. 2007; 27:7125–7142. [PubMed: 17698582]

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Sichter
(Hindemith), SleepyHollow02

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