孕酮受體
位於11號人類染色體的基因
孕酮受體(英語:progesterone receptor,縮寫PR,也被稱為NR3C3 ,nuclear receptor subfamily 3, group C, member 3,即核受體第三亞族C組成員3)是一種細胞內蛋白質,由甾體激素孕酮激活。
在人體中,孕酮受體由基因PGR 編碼,位於11號染色體長臂22區[1][2][3],能通過選擇性剪接形成兩種蛋白異形體A和B,有著各自不同的分子量[4][5][6]。
功能
編輯孕酮是引起孕酮受體反應的配體,在孕酮受體的C端未結合該激素時,與其相關的DNA片段的轉錄處於抑制狀態。在與激素結合後,孕酮受體會變構並開始起作用。而孕酮受體的受體拮抗劑會阻止這種結構改變。
在孕酮與其受體結合後,孕酮受體變構並發生二聚化,緊接著以複合體形式進入細胞核與相關的DNA結合,從而使其開始轉錄,合成mRNA,並表達為相關蛋白質。
結構
編輯Progesterone receptor, N-terminal | |||||||||
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鑑定 | |||||||||
標誌 | Progest_rcpt_N | ||||||||
Pfam | PF02161(舊版) | ||||||||
InterPro | IPR000128 | ||||||||
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和其它甾體激素受體類似,孕酮受體的N端有一個調控結構域,一個DNA結合結構域,以及一個鉸鏈區,在C端有一個配體結合結構域。異形體B比異形體A多一個TAF-3區域。
交互作用
編輯孕酮受體能與下列蛋白質發生交互作用:
另見
編輯參考文獻
編輯- ^ Misrahi M, Atger M, d'Auriol L, Loosfelt H, Meriel C, Fridlansky F, Guiochon-Mantel A, Galibert F, Milgrom E. Complete amino acid sequence of the human progesterone receptor deduced from cloned cDNA. Biochem. Biophys. Res. Commun. March 1987, 143 (2): 740–8. PMID 3551956. doi:10.1016/0006-291X(87)91416-1.
- ^ Law ML, Kao FT, Wei Q, Hartz JA, Greene GL, Zarucki-Schulz T, Conneely OM, Jones C, Puck TT, O'Malley BW. The progesterone receptor gene maps to human chromosome band 11q13, the site of the mammary oncogene int-2. Proc. Natl. Acad. Sci. U.S.A. May 1987, 84 (9): 2877–81. PMC 304763 . PMID 3472240. doi:10.1073/pnas.84.9.2877.
- ^ ensembl.org, Gene: ESR1 (ENSG00000091831). [2014-06-28]. (原始內容存檔於2022-01-05).
- ^ Gadkar-Sable S, Shah C, Rosario G, Sachdeva G, Puri C. Progesterone receptors: various forms and functions in reproductive tissues. Front. Biosci. 2005, 10: 2118–30. PMID 15970482. doi:10.2741/1685.
- ^ Kase, Nathan G.; Speroff, Leon; Glass, Robert L. Clinical gynecologic endocrinology and infertility. Hagerstown, MD: Lippincott Williams & Wilkins. 1999. ISBN 0-683-30379-1.
- ^ Fritz, Marc A.; Speroff, Leon. Clinical gynecologic endocrinology and infertility. Hagerstown, MD: Lippincott Williams & Wilkins. 2005. ISBN 0-7817-4795-3.
- ^ Zhang XL, Zhang D, Michel FJ, Blum JL, Simmen FA, Simmen RC. Selective interactions of Kruppel-like factor 9/basic transcription element-binding protein with progesterone receptor isoforms A and B determine transcriptional activity of progesterone-responsive genes in endometrial epithelial cells. J. Biol. Chem. June 2003, 278 (24): 21474–82. PMID 12672823. doi:10.1074/jbc.M212098200.
- ^ Giangrande PH, Kimbrel EA, Edwards DP, McDonnell DP. The opposing transcriptional activities of the two isoforms of the human progesterone receptor are due to differential cofactor binding. Mol. Cell. Biol. May 2000, 20 (9): 3102–15. PMC 85605 . PMID 10757795. doi:10.1128/MCB.20.9.3102-3115.2000.
- ^ Nawaz Z, Lonard DM, Smith CL, Lev-Lehman E, Tsai SY, Tsai MJ, O'Malley BW. The Angelman syndrome-associated protein, E6-AP, is a coactivator for the nuclear hormone receptor superfamily. Mol. Cell. Biol. February 1999, 19 (2): 1182–9. PMC 116047 . PMID 9891052.
延伸閱讀
編輯- Butnor KJ, Burchette JL, Robboy SJ. Progesterone receptor activity in leiomyomatosis peritonealis disseminata. Int. J. Gynecol. Pathol. 2002, 18 (3): 259–64. PMID 12090595. doi:10.1097/00004347-199907000-00012.
- Leonhardt SA, Boonyaratanakornkit V, Edwards DP. Progesterone receptor transcription and non-transcription signaling mechanisms. Steroids. 2004, 68 (10–13): 761–70. PMID 14667966. doi:10.1016/S0039-128X(03)00129-6.
- Conneely OM, Mulac-Jericevic B, Lydon JP. Progesterone-dependent regulation of female reproductive activity by two distinct progesterone receptor isoforms. Steroids. 2004, 68 (10–13): 771–8. PMID 14667967. doi:10.1016/S0039-128X(03)00126-0.
- Bagchi MK, Tsai SY, Tsai MJ, O'Malley BW. Ligand and DNA-dependent phosphorylation of human progesterone receptor in vitro. Proc. Natl. Acad. Sci. U.S.A. 1992, 89 (7): 2664–8. PMC 48722 . PMID 1557371. doi:10.1073/pnas.89.7.2664.
- Kastner P, Krust A, Turcotte B; et al. Two distinct estrogen-regulated promoters generate transcripts encoding the two functionally different human progesterone receptor forms A and B. EMBO J. 1990, 9 (5): 1603–14. PMC 551856 . PMID 2328727.
- Guiochon-Mantel A, Loosfelt H, Lescop P; et al. Mechanisms of nuclear localization of the progesterone receptor: evidence for interaction between monomers. Cell. 1989, 57 (7): 1147–54. PMID 2736623. doi:10.1016/0092-8674(89)90052-4.
- Fernandez MD, Carter GD, Palmer TN. The interaction of canrenone with oestrogen and progesterone receptors in human uterine cytosol. British Journal of Clinical Pharmacology. 1983, 15 (1): 95–101. PMC 1427833 . PMID 6849751. doi:10.1111/j.1365-2125.1983.tb01470.x.
- Oñate SA, Tsai SY, Tsai MJ, O'Malley BW. Sequence and characterization of a coactivator for the steroid hormone receptor superfamily. Science. 1995, 270 (5240): 1354–7. PMID 7481822. doi:10.1126/science.270.5240.1354.
- Zhang Y, Beck CA, Poletti A; et al. Identification of phosphorylation sites unique to the B form of human progesterone receptor. In vitro phosphorylation by casein kinase II. J. Biol. Chem. 1995, 269 (49): 31034–40. PMID 7983041.
- Mansour I, Reznikoff-Etievant MF, Netter A. No evidence for the expression of the progesterone receptor on peripheral blood lymphocytes during pregnancy. Hum. Reprod. 1995, 9 (8): 1546–9. PMID 7989520.
- Kalkhoven E, Wissink S, van der Saag PT, van der Burg B. Negative interaction between the RelA(p65) subunit of NF-kappaB and the progesterone receptor. J. Biol. Chem. 1996, 271 (11): 6217–24. PMID 8626413. doi:10.1074/jbc.271.11.6217.
- Wang JD, Zhu JB, Fu Y; et al. Progesterone receptor immunoreactivity at the maternofetal interface of first trimester pregnancy: a study of the trophoblast population. Hum. Reprod. 1996, 11 (2): 413–9. PMID 8671234. doi:10.1093/humrep/11.2.413.
- Thénot S, Henriquet C, Rochefort H, Cavaillès V. Differential interaction of nuclear receptors with the putative human transcriptional coactivator hTIF1. J. Biol. Chem. 1997, 272 (18): 12062–8. PMID 9115274. doi:10.1074/jbc.272.18.12062.
- Jenster G, Spencer TE, Burcin MM; et al. Steroid receptor induction of gene transcription: a two-step model. Proc. Natl. Acad. Sci. U.S.A. 1997, 94 (15): 7879–84. PMC 21523 . PMID 9223281. doi:10.1073/pnas.94.15.7879.
- Shanker YG, Sharma SC, Rao AJ. Expression of progesterone receptor mRNA in the first trimester human placenta. Biochem. Mol. Biol. Int. 1997, 42 (6): 1235–40. PMID 9305541.
- Richer JK, Lange CA, Wierman AM; et al. Progesterone receptor variants found in breast cells repress transcription by wild-type receptors. Breast Cancer Res. Treat. 1998, 48 (3): 231–41. PMID 9598870. doi:10.1023/A:1005941117247.
- Williams SP, Sigler PB. Atomic structure of progesterone complexed with its receptor. Nature. 1998, 393 (6683): 392–6. PMID 9620806. doi:10.1038/30775.
- Boonyaratanakornkit V, Melvin V, Prendergast P; et al. High-mobility group chromatin proteins 1 and 2 functionally interact with steroid hormone receptors to enhance their DNA binding in vitro and transcriptional activity in mammalian cells. Mol. Cell. Biol. 1998, 18 (8): 4471–87. PMC 109033 . PMID 9671457.
- Nawaz Z, Lonard DM, Smith CL; et al. The Angelman syndrome-associated protein, E6-AP, is a coactivator for the nuclear hormone receptor superfamily. Mol. Cell. Biol. 1999, 19 (2): 1182–9. PMC 116047 . PMID 9891052.