SCARB1
Scavenger receptor class B member 1 (SRB1) also known as SR-BI is a protein that in humans is encoded by the SCARB1 gene.[5] SR-BI functions as a receptor for high-density lipoprotein.[6]
Function
Scavenger receptor class B, type I (SR-BI) is an integral membrane protein found in numerous cell types/tissues, including the liver and adrenal. It is best known for its role in facilitating the uptake of cholesteryl esters from high-density lipoproteins in the liver. This process drives the movement of cholesterol from peripheral tissues towards the liver, where cholesterol can either be secreted via the bile duct or be used to synthesise steroid hormones.[7] This movement of cholesterol is known as reverse cholesterol transport and is a protective mechanism against the development of atherosclerosis, which is the principal cause of heart disease and stroke.
SR-BI is crucial in lipid soluble vitamin uptake.[8]
In melanocytic cells SCARB1 gene expression may be regulated by the MITF.[9]
Species distribution
SR-BI has also been identified in the livers of non-mammalian species (turtle, goldfish, shark, chicken, frog, and skate), suggesting it emerged early in vertebrate evolutionary history. The turtle also seems to upregulate SB-RI during egg development, indicating that cholesterol efflux may be at peak levels during developmental stages.[10]
Clinical significance
SCARB1 along with CD81 is the receptor for the entry of the Hepatitis C virus into liver cells.[11]
Preclinical research
Although malignant tumors are known to display extreme heterogeneity, overexpression of SR-B1 is a relatively consistent marker in cancerous tissues. While SR-B1 normally mediates the transfer of cholesterol between high-density lipoproteins (HDL) and healthy cells, it also facilitates the selective uptake of cholesterol by malignant cells. In this way, upregulation of the SR-B1 receptor becomes an enabling factor for self-sufficient proliferation in cancerous tissue.[12][13]
SR-B1 mediated delivery has also been used in the transfection of cancer cells with siRNA, or small interfering RNAs. This therapy causes RNA interference, in which short segments of double stranded RNA acts to silence targeted oncogenes post-transcription. SR-B1 mediation reduces siRNA degradation and off-target accumulation while enhancing delivery to targeted tissues. In "metastatic and taxane-resistant models of ovarian cancer, rHDL-mediated siren delivery improved responses.[14]
Interactive pathway map
Click on genes, proteins and metabolites below to link to respective articles. [§ 1]
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Statin Pathway edit
- ↑ The interactive pathway map can be edited at WikiPathways: "Statin_Pathway_WP430".
References
- 1 2 3 GRCh38: Ensembl release 89: ENSG00000073060 - Ensembl, May 2017
- 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000037936 - Ensembl, May 2017
- ↑ "Human PubMed Reference:".
- ↑ "Mouse PubMed Reference:".
- ↑ "Entrez Gene: SCARB1 Scavenger receptor class B, member 1".
- ↑ Acton S, Rigotti A, Landschulz KT, Xu S, Hobbs HH, Krieger M (January 1996). "Identification of scavenger receptor SR-BI as a high density lipoprotein receptor". Science. 271 (5248): 518–20. PMID 8560269. doi:10.1126/science.271.5248.518.
- ↑ Rhainds D, Brissette L (January 2004). "The role of scavenger receptor class B type I (SR-BI) in lipid trafficking. defining the rules for lipid traders". The International Journal of Biochemistry & Cell Biology. 36 (1): 39–77. PMID 14592533.
- ↑ Valacchi G, Sticozzi C, Lim Y, Pecorelli A (July 2011). "Scavenger receptor class B type I: a multifunctional receptor". Annals of the New York Academy of Sciences. 1229: E1–7. PMID 22239457. doi:10.1111/j.1749-6632.2011.06205.x.
- ↑ Hoek KS, Schlegel NC, Eichhoff OM, Widmer DS, Praetorius C, Einarsson SO, Valgeirsdottir S, Bergsteinsdottir K, Schepsky A, Dummer R, Steingrimsson E (December 2008). "Novel MITF targets identified using a two-step DNA microarray strategy". Pigment Cell & Melanoma Research. 21 (6): 665–76. PMID 19067971. doi:10.1111/j.1755-148X.2008.00505.x.
- ↑ Duggan AE, Marie RS, Callard IP (April 2002). "Expression of SR-BI (Scavenger Receptor Class B Type I) in turtle (Chrysemys picta) tissues and other nonmammalian vertebrates". The Journal of Experimental Zoology. 292 (5): 430–4. PMID 11857477. doi:10.1002/jez.10067.
- ↑ Kapadia SB, Barth H, Baumert T, McKeating JA, Chisari FV (January 2007). "Initiation of hepatitis C virus infection is dependent on cholesterol and cooperativity between CD81 and scavenger receptor B type I". Journal of Virology. 81 (1): 374–83. PMC 1797271
. PMID 17050612. doi:10.1128/JVI.01134-06. - ↑ Mooberry LK, Sabnis NA, Panchoo M, Nagarajan B, Lacko AG (December 2016). "Targeting the SR-B1 Receptor as a Gateway for Cancer Therapy and Imaging". Frontiers in Pharmacology. 7 (466): 466. PMID 28018216. doi:10.3389/fphar.2016.00466.
- ↑ Gutierrez-Pajares JL, Ben Hassen C, Chevalier S, Frank PG (2016). "SR-BI: Linking Cholesterol and Lipoprotein Metabolism with Breast and Prostate Cancer". Frontiers in Pharmacology. 7: 338. PMC 5054001 . PMID 27774064. doi:10.3389/fphar.2016.00338.
- ↑ Rajora MA, Zheng G (2016). "Targeting SR-BI for Cancer Diagnostics, Imaging and Therapy". Frontiers in Pharmacology. 7 (Art. 326): 326. PMID 27729859. doi:10.3389/fphar.2016.00326.
Further reading
- Williams DL, Temel RE, Connelly MA (November 2000). "Roles of scavenger receptor BI and APO A-I in selective uptake of HDL cholesterol by adrenal cells". Endocrine Research. 26 (4): 639–51. PMID 11196441. doi:10.3109/07435800009048584.
- Krause BR, Auerbach BJ (March 2001). "Reverse cholesterol transport and future pharmacological approaches to the treatment of atherosclerosis". Current Opinion in Investigational Drugs. 2 (3): 375–81. PMID 11575708.
- Connelly MA, Williams DL (June 2004). "Scavenger receptor BI: a scavenger receptor with a mission to transport high density lipoprotein lipids". Current Opinion in Lipidology. 15 (3): 287–95. PMID 15166784. doi:10.1097/00041433-200406000-00008.
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- Calvo D, Dopazo J, Vega MA (January 1995). "The CD36, CLA-1 (CD36L1), and LIMPII (CD36L2) gene family: cellular distribution, chromosomal location, and genetic evolution". Genomics. 25 (1): 100–6. PMID 7539776. doi:10.1016/0888-7543(95)80114-2.
- Calvo D, Vega MA (September 1993). "Identification, primary structure, and distribution of CLA-1, a novel member of the CD36/LIMPII gene family". The Journal of Biological Chemistry. 268 (25): 18929–35. PMID 7689561.
- Murao K, Terpstra V, Green SR, Kondratenko N, Steinberg D, Quehenberger O (July 1997). "Characterization of CLA-1, a human homologue of rodent scavenger receptor BI, as a receptor for high density lipoprotein and apoptotic thymocytes". The Journal of Biological Chemistry. 272 (28): 17551–7. PMID 9211901. doi:10.1074/jbc.272.28.17551.
- Ikemoto M, Arai H, Feng D, Tanaka K, Aoki J, Dohmae N, Takio K, Adachi H, Tsujimoto M, Inoue K (June 2000). "Identification of a PDZ-domain-containing protein that interacts with the scavenger receptor class B type I". Proceedings of the National Academy of Sciences of the United States of America. 97 (12): 6538–43. PMC 18651 . PMID 10829064. doi:10.1073/pnas.100114397.
- Husemann J, Silverstein SC (March 2001). "Expression of scavenger receptor class B, type I, by astrocytes and vascular smooth muscle cells in normal adult mouse and human brain and in Alzheimer's disease brain". The American Journal of Pathology. 158 (3): 825–32. PMC 1850374 . PMID 11238031. doi:10.1016/S0002-9440(10)64030-8.
- Li XA, Titlow WB, Jackson BA, Giltiay N, Nikolova-Karakashian M, Uittenbogaard A, Smart EJ (March 2002). "High density lipoprotein binding to scavenger receptor, Class B, type I activates endothelial nitric-oxide synthase in a ceramide-dependent manner". The Journal of Biological Chemistry. 277 (13): 11058–63. PMID 11792700. doi:10.1074/jbc.M110985200.
- Duncan KG, Bailey KR, Kane JP, Schwartz DM (April 2002). "Human retinal pigment epithelial cells express scavenger receptors BI and BII". Biochemical and Biophysical Research Communications. 292 (4): 1017–22. PMID 11944916. doi:10.1006/bbrc.2002.6756.
- Kawasaki Y, Nakagawa A, Nagaosa K, Shiratsuchi A, Nakanishi Y (July 2002). "Phosphatidylserine binding of class B scavenger receptor type I, a phagocytosis receptor of testicular sertoli cells". The Journal of Biological Chemistry. 277 (30): 27559–66. PMID 12016218. doi:10.1074/jbc.M202879200.
- Qi C, Chang J, Zhu Y, Yeldandi AV, Rao SM, Zhu YJ (August 2002). "Identification of protein arginine methyltransferase 2 as a coactivator for estrogen receptor alpha". The Journal of Biological Chemistry. 277 (32): 28624–30. PMID 12039952. doi:10.1074/jbc.M201053200.
- Johnson MS, Svensson PA, Borén J, Billig H, Carlsson LM, Carlsson B (June 2002). "Expression of scavenger receptor class B type I in gallbladder columnar epithelium". Journal of Gastroenterology and Hepatology. 17 (6): 713–20. PMID 12100619. doi:10.1046/j.1440-1746.2002.02776.x.
- Silver DL (September 2002). "A carboxyl-terminal PDZ-interacting domain of scavenger receptor B, type I is essential for cell surface expression in liver". The Journal of Biological Chemistry. 277 (37): 34042–7. PMID 12119305. doi:10.1074/jbc.M206584200.
- Bultel-Brienne S, Lestavel S, Pilon A, Laffont I, Tailleux A, Fruchart JC, Siest G, Clavey V (September 2002). "Lipid free apolipoprotein E binds to the class B Type I scavenger receptor I (SR-BI) and enhances cholesteryl ester uptake from lipoproteins". The Journal of Biological Chemistry. 277 (39): 36092–9. PMID 12138091. doi:10.1074/jbc.M201943200.
- Strauss JG, Zimmermann R, Hrzenjak A, Zhou Y, Kratky D, Levak-Frank S, Kostner GM, Zechner R, Frank S (November 2002). "Endothelial cell-derived lipase mediates uptake and binding of high-density lipoprotein (HDL) particles and the selective uptake of HDL-associated cholesterol esters independent of its enzymic activity". The Biochemical Journal. 368 (Pt 1): 69–79. PMC 1222966 . PMID 12164779. doi:10.1042/BJ20020306.