“Small heterodimer partner”的意思、由来-开放百科全书

The small heterodimer partner (SHP) also known as NR0B2 (nuclear receptor subfamily 0, group B, member 2) is a protein that in humans is encoded by the NR0B2 gene.^[1] SHP is a member of the nuclear receptor family of intracellular transcription factors.^[2] SHP is unusual for a nuclear receptor in that it lacks a DNA binding domain. Therefore, it is technically neither a transcription factor nor nuclear receptor but nevertheless it is still classified as such due to relatively high sequence homology with other nuclear receptor family members.

Function

The principal role of SHP appears to be repression of other nuclear receptors through association to produce a non-productive heterodimer.^[3] The protein has also been identified as a mediating factor in the metabolic circadian clock ^[4] Research shows that it interacts with retinoid and thyroid hormone receptors, inhibiting their ligand-dependent transcriptional activation. In addition, interaction with estrogen receptors has been demonstrated, leading to inhibition of function. Studies suggest that the protein represses nuclear hormone receptor-mediated transactivation via two separate steps: competition with coactivators and the direct effects of its transcriptional repressor function.^[1]

Interactions

References

1. ^¹{{cite web | title = Entrez Gene: NR0B2 nuclear receptor subfamily 0, group B, member 2| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=8431| accessdate = }}
2. ^{{cite journal | vauthors = Lee HK, Lee YK, Park SH, Kim YS, Park SH, Lee JW, Kwon HB, Soh J, Moore DD, Choi HS | title = Structure and expression of the orphan nuclear receptor SHP gene | journal = The Journal of Biological Chemistry | volume = 273 | issue = 23 | pages = 14398–402 | date = Jun 1998 | pmid = 9603951 | doi = 10.1074/jbc.273.23.14398 }}
3. ^{{cite journal | vauthors = Båvner A, Sanyal S, Gustafsson JA, Treuter E | title = Transcriptional corepression by SHP: molecular mechanisms and physiological consequences | journal = Trends in Endocrinology and Metabolism | volume = 16 | issue = 10 | pages = 478–88 | date = Dec 2005 | pmid = 16275121 | doi = 10.1016/j.tem.2005.10.005 }}
4. ^{{cite journal | vauthors = Wu N, Kang HK, Zhou Y, Lee JM, Kettner NM, Mamrosh JL, Choi S, Fu L, Moore DD | title = Small heterodimer partner (NR0B2) coordinates nutrient signaling and the circadian clock in mice | journal = Molecular Endocrinology | volume = 30 | issue = 9 | pages = 988–95 | date = Jul 2016 | doi = 10.1210/me.2015-1295 | pmid = 27427832 | pmc = 5004116 }}
5. ^{{cite journal | vauthors = Gobinet J, Auzou G, Nicolas JC, Sultan C, Jalaguier S | title = Characterization of the interaction between androgen receptor and a new transcriptional inhibitor, SHP | journal = Biochemistry | volume = 40 | issue = 50 | pages = 15369–77 | date = Dec 2001 | pmid = 11735420 | doi = 10.1021/bi011384o }}
6. ^{{cite journal | vauthors = Klinge CM, Jernigan SC, Risinger KE | title = The agonist activity of tamoxifen is inhibited by the short heterodimer partner orphan nuclear receptor in human endometrial cancer cells | journal = Endocrinology | volume = 143 | issue = 3 | pages = 853–67 | date = Mar 2002 | pmid = 11861507 | doi = 10.1210/en.143.3.853 }}
7. ^¹{{cite journal | vauthors = Lee YK, Dell H, Dowhan DH, Hadzopoulou-Cladaras M, Moore DD | title = The orphan nuclear receptor SHP inhibits hepatocyte nuclear factor 4 and retinoid X receptor transactivation: two mechanisms for repression | journal = Molecular and Cellular Biology | volume = 20 | issue = 1 | pages = 187–95 | date = Jan 2000 | pmid = 10594021 | pmc = 85074 | doi = 10.1128/MCB.20.1.187-195.2000 }}
8. ^{{cite journal | vauthors = Lee YK, Moore DD | title = Dual mechanisms for repression of the monomeric orphan receptor liver receptor homologous protein-1 by the orphan small heterodimer partner | journal = The Journal of Biological Chemistry | volume = 277 | issue = 4 | pages = 2463–7 | date = Jan 2002 | pmid = 11668176 | doi = 10.1074/jbc.M105161200 }}
9. ^¹²{{cite journal | vauthors = Brendel C, Schoonjans K, Botrugno OA, Treuter E, Auwerx J | title = The small heterodimer partner interacts with the liver X receptor alpha and represses its transcriptional activity | journal = Molecular Endocrinology | volume = 16 | issue = 9 | pages = 2065–76 | date = Sep 2002 | pmid = 12198243 | doi = 10.1210/me.2001-0194 }}
10. ^{{cite journal | vauthors = Nishizawa H, Yamagata K, Shimomura I, Takahashi M, Kuriyama H, Kishida K, Hotta K, Nagaretani H, Maeda N, Matsuda M, Kihara S, Nakamura T, Nishigori H, Tomura H, Moore DD, Takeda J, Funahashi T, Matsuzawa Y | title = Small heterodimer partner, an orphan nuclear receptor, augments peroxisome proliferator-activated receptor gamma transactivation | journal = The Journal of Biological Chemistry | volume = 277 | issue = 2 | pages = 1586–92 | date = Jan 2002 | pmid = 11696534 | doi = 10.1074/jbc.M104301200 }}
11. ^{{cite journal | vauthors = Seol W, Choi HS, Moore DD | title = An orphan nuclear hormone receptor that lacks a DNA binding domain and heterodimerizes with other receptors | journal = Science | volume = 272 | issue = 5266 | pages = 1336–9 | date = May 1996 | pmid = 8650544 | doi = 10.1126/science.272.5266.1336 }}
12. ^{{cite journal | vauthors = Seol W, Hanstein B, Brown M, Moore DD | title = Inhibition of estrogen receptor action by the orphan receptor SHP (short heterodimer partner) | journal = Molecular Endocrinology | volume = 12 | issue = 10 | pages = 1551–7 | date = Oct 1998 | pmid = 9773978 | doi = 10.1210/me.12.10.1551 }}

Further reading

{{cite journal | vauthors = Seol W, Choi HS, Moore DD | title = An orphan nuclear hormone receptor that lacks a DNA binding domain and heterodimerizes with other receptors | journal = Science | volume = 272 | issue = 5266 | pages = 1336–9 | date = May 1996 | pmid = 8650544 | doi = 10.1126/science.272.5266.1336 }}

{{cite journal | vauthors = Seol W, Hanstein B, Brown M, Moore DD | title = Inhibition of estrogen receptor action by the orphan receptor SHP (short heterodimer partner) | journal = Molecular Endocrinology | volume = 12 | issue = 10 | pages = 1551–7 | date = Oct 1998 | pmid = 9773978 | doi = 10.1210/me.12.10.1551 }}

{{cite journal | vauthors = Lee YK, Dell H, Dowhan DH, Hadzopoulou-Cladaras M, Moore DD | title = The orphan nuclear receptor SHP inhibits hepatocyte nuclear factor 4 and retinoid X receptor transactivation: two mechanisms for repression | journal = Molecular and Cellular Biology | volume = 20 | issue = 1 | pages = 187–95 | date = Jan 2000 | pmid = 10594021 | pmc = 85074 | doi = 10.1128/MCB.20.1.187-195.2000 }}

{{cite journal | vauthors = Johansson L, Båvner A, Thomsen JS, Färnegårdh M, Gustafsson JA, Treuter E | title = The orphan nuclear receptor SHP utilizes conserved LXXLL-related motifs for interactions with ligand-activated estrogen receptors | journal = Molecular and Cellular Biology | volume = 20 | issue = 4 | pages = 1124–33 | date = Feb 2000 | pmid = 10648597 | pmc = 85230 | doi = 10.1128/MCB.20.4.1124-1133.2000 }}

{{cite journal | vauthors = Lu TT, Makishima M, Repa JJ, Schoonjans K, Kerr TA, Auwerx J, Mangelsdorf DJ | title = Molecular basis for feedback regulation of bile acid synthesis by nuclear receptors | journal = Molecular Cell | volume = 6 | issue = 3 | pages = 507–15 | date = Sep 2000 | pmid = 11030331 | doi = 10.1016/S1097-2765(00)00050-2 }}

{{cite journal | vauthors = Nishigori H, Tomura H, Tonooka N, Kanamori M, Yamada S, Sho K, Inoue I, Kikuchi N, Onigata K, Kojima I, Kohama T, Yamagata K, Yang Q, Matsuzawa Y, Miki T, Seino S, Kim MY, Choi HS, Lee YK, Moore DD, Takeda J | title = Mutations in the small heterodimer partner gene are associated with mild obesity in Japanese subjects | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 98 | issue = 2 | pages = 575–80 | date = Jan 2001 | pmid = 11136233 | pmc = 14629 | doi = 10.1073/pnas.021544398 }}

{{cite journal | vauthors = Lee YK, Moore DD | title = Dual mechanisms for repression of the monomeric orphan receptor liver receptor homologous protein-1 by the orphan small heterodimer partner | journal = The Journal of Biological Chemistry | volume = 277 | issue = 4 | pages = 2463–7 | date = Jan 2002 | pmid = 11668176 | doi = 10.1074/jbc.M105161200 }}

{{cite journal | vauthors = Nishizawa H, Yamagata K, Shimomura I, Takahashi M, Kuriyama H, Kishida K, Hotta K, Nagaretani H, Maeda N, Matsuda M, Kihara S, Nakamura T, Nishigori H, Tomura H, Moore DD, Takeda J, Funahashi T, Matsuzawa Y | title = Small heterodimer partner, an orphan nuclear receptor, augments peroxisome proliferator-activated receptor gamma transactivation | journal = The Journal of Biological Chemistry | volume = 277 | issue = 2 | pages = 1586–92 | date = Jan 2002 | pmid = 11696534 | doi = 10.1074/jbc.M104301200 }}

{{cite journal | vauthors = Sanyal S, Kim JY, Kim HJ, Takeda J, Lee YK, Moore DD, Choi HS | title = Differential regulation of the orphan nuclear receptor small heterodimer partner (SHP) gene promoter by orphan nuclear receptor ERR isoforms | journal = The Journal of Biological Chemistry | volume = 277 | issue = 3 | pages = 1739–48 | date = Jan 2002 | pmid = 11705994 | doi = 10.1074/jbc.M106140200 }}

{{cite journal | vauthors = Gobinet J, Auzou G, Nicolas JC, Sultan C, Jalaguier S | title = Characterization of the interaction between androgen receptor and a new transcriptional inhibitor, SHP | journal = Biochemistry | volume = 40 | issue = 50 | pages = 15369–77 | date = Dec 2001 | pmid = 11735420 | doi = 10.1021/bi011384o }}

{{cite journal | vauthors = Klinge CM, Jernigan SC, Risinger KE | title = The agonist activity of tamoxifen is inhibited by the short heterodimer partner orphan nuclear receptor in human endometrial cancer cells | journal = Endocrinology | volume = 143 | issue = 3 | pages = 853–67 | date = Mar 2002 | pmid = 11861507 | doi = 10.1210/en.143.3.853 }}

{{cite journal | vauthors = Ogata M, Awaji T, Iwasaki N, Miyazaki S, Bell GI, Iwamoto Y | title = Nuclear translocation of SHP and visualization of interaction with HNF-4alpha in living cells | journal = Biochemical and Biophysical Research Communications | volume = 292 | issue = 1 | pages = 8–12 | date = Mar 2002 | pmid = 11890664 | doi = 10.1006/bbrc.2002.6593 }}

{{cite journal | vauthors = Cao H, Hegele RA | title = Identification of polymorphisms in the human SHP1 gene | journal = Journal of Human Genetics | volume = 47 | issue = 8 | pages = 445–7 | year = 2002 | pmid = 12181644 | doi = 10.1007/s100380200062 }}

{{cite journal | vauthors = Brendel C, Schoonjans K, Botrugno OA, Treuter E, Auwerx J | title = The small heterodimer partner interacts with the liver X receptor alpha and represses its transcriptional activity | journal = Molecular Endocrinology | volume = 16 | issue = 9 | pages = 2065–76 | date = Sep 2002 | pmid = 12198243 | doi = 10.1210/me.2001-0194 }}

{{cite journal | vauthors = Borgius LJ, Steffensen KR, Gustafsson JA, Treuter E | title = Glucocorticoid signaling is perturbed by the atypical orphan receptor and corepressor SHP | journal = The Journal of Biological Chemistry | volume = 277 | issue = 51 | pages = 49761–6 | date = Dec 2002 | pmid = 12324453 | doi = 10.1074/jbc.M205641200 }}

{{cite journal | vauthors = Hung CC, Farooqi IS, Ong K, Luan J, Keogh JM, Pembrey M, Yeo GS, Dunger D, Wareham NJ, O' Rahilly S | title = Contribution of variants in the small heterodimer partner gene to birthweight, adiposity, and insulin levels: mutational analysis and association studies in multiple populations | journal = Diabetes | volume = 52 | issue = 5 | pages = 1288–91 | date = May 2003 | pmid = 12716767 | doi = 10.2337/diabetes.52.5.1288 }}

{{cite journal | vauthors = Lai K, Harnish DC, Evans MJ | title = Estrogen receptor alpha regulates expression of the orphan receptor small heterodimer partner | journal = The Journal of Biological Chemistry | volume = 278 | issue = 38 | pages = 36418–29 | date = Sep 2003 | pmid = 12842887 | doi = 10.1074/jbc.M303913200 }}

{{cite journal | vauthors = Kovacic A, Speed CJ, Simpson ER, Clyne CD | title = Inhibition of aromatase transcription via promoter II by short heterodimer partner in human preadipocytes | journal = Molecular Endocrinology | volume = 18 | issue = 1 | pages = 252–9 | date = Jan 2004 | pmid = 14593077 | doi = 10.1210/me.2003-0211 }}

Function

Interactions

References

Further reading

External links