Protein Phosphatase 2A (PP2A) regulates low density lipoprotein uptake through regulating Sterol Response Element-binding Protein-2 (SREBP-2) DNA binding

Journal of Biological Chemistry

Volumn 289, Issue 24, 2014, Pages 17268-17279

  Rice, Lyndi M ^a   Donigan, Melissa ^b   Yang, Muhua ^b   Liu, Weidong ^b   Pandya, Devanshi ^b   Joseph, Biny K ^b   Sodi, Valerie ^a   Gearhart, Tricia L ^c   Yip, Jenny ^b   Bouchard, Michael ^c   Nickels Jr , Joseph T ^b  

^a Medical Diagnostic Laboratories   (United States)

^b Genesis Biotechnology Group   (United States)

^c DREXEL UNIVERSITY COLLEGE OF MEDICINE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ALCOHOLS; PHOSPHATASES; PROTEINS; TRANSCRIPTION;

CHOLESTEROL HOMEOSTASIS; ELEMENT-BINDING PROTEINS; HMG-COA REDUCTASE INHIBITOR; LOW DENSITY LIPOPROTEINS; NUCLEAR TRANSLOCATIONS; PHOSPHORYLATION SITES; PROTEIN PHOSPHATASE 2A; TRANSCRIPTIONAL LEVELS;

CHOLESTEROL;

CHOLESTEROL; DNA; LOW DENSITY LIPOPROTEIN; LOW DENSITY LIPOPROTEIN RECEPTOR; MEVINOLIN; OKADAIC ACID; PHOSPHOPROTEIN PHOSPHATASE 2A; SMALL INTERFERING RNA; STEROL REGULATORY ELEMENT BINDING PROTEIN 2;

ARTICLE; CELL FRACTIONATION; CHROMATIN IMMUNOPRECIPITATION; CONTROLLED STUDY; DEPLETION; ENZYME ACTIVITY; FLUORESCENCE MICROSCOPY; GEL MOBILITY SHIFT ASSAY; GENE EXPRESSION; HEPG2 CELL LINE; HOMEOSTASIS; HUMAN; HUMAN CELL; IMMUNOCYTOCHEMISTRY; LDLR GENE; PLASMID; PRIORITY JOURNAL; PROMOTER REGION; PROTEIN CLEAVAGE; PROTEIN DNA BINDING; PROTEIN PHOSPHORYLATION; PROTEIN STABILITY; REGULATORY MECHANISM; REVERSE TRANSCRIPTION POLYMERASE CHAIN REACTION; RNA EXTRACTION;

CHOLESTEROL; DNA; LIPID; LIPOPROTEIN; LOW DENSITY LIPOPROTEIN (LDL); METABOLISM; SREBP; TRANSCRIPTION;

ACTIVE TRANSPORT, CELL NUCLEUS; CHOLESTEROL, LDL; HEK293 CELLS; HEP G2 CELLS; HUMANS; PROTEIN BINDING; PROTEIN PHOSPHATASE 2; RECEPTORS, LDL; RESPONSE ELEMENTS; STEROL REGULATORY ELEMENT BINDING PROTEIN 2;

EID: 84902439487     PISSN: 00219258     EISSN: 1083351X     Source Type: Journal    
DOI: 10.1074/jbc.M114.570390     Document Type: Article

References (66)

1. Maxfield, F. R., and Tabas, I. (2005) Role of cholesterol and lipid and organization in disease. Nature 438, 612-621 (Pubitemid 41740565)
2. Sonnino, S., and Prinetti, A. (2013) Membrane domains and the "lipid raft" concept. Curr. Med. Chem. 20, 4-21
3. Wood, W. G., Igbavboa, U., Müller, W. E., and Eckert, G. P. (2011) Cholesterol asymmetry in synaptic plasma membranes. J. Neurochem. 116, 684-689
4. Elson, E. L., Fried, E., Dolbow, J. E., and Genin, G. M. (2010) Phase separation in biological membranes. Integration of theory and experiment. Annu. Rev. Biophys. 39, 207-226
5. Incardona, J. P., and Eaton, S. (2000) Cholesterol in Signal Transduction. Curr. Opin. Cell Biol. 12, 193-203 (Pubitemid 30142566)
6. Sato, K. (2008) Signal transduction of fertilization in frog eggs and antiapoptotic mechanism in human cancer cells: common and specific functions of membrane microdomains. Open Biochem. J. 2, 49-59
7. Breitling, R. (2007) Greased hedgehogs: new links between hedgehog signaling and cholesterol metabolism. Bioessays 29, 1085-1094
8. Illingworth, D. R. (2000) Management of hypercholestrolemia. Med. Clin. North Am. 84, 23-42
9. Stein O, Stein, Y. (2005) Lipid transfer proteins (LTP) and atherosclerosis. Atherosclerosis 178, 217-230 (Pubitemid 40193434)
10. Ni Chróinin, D., Asplund, K., Åsberg, S., Callaly, E., Cuadrado-Godia, E., Díez-Tejedor, E., Di Napoli, M., Engelter, S. T., Furie, K. L., Giannopoulos, S., Gotto, A. M., Jr., Hannon, N., Jonsson, F., Kapral, M. K., Martí-Fàbregas, J., Martínez-Sanchez, P., Milionis, H. J., Montaner, J., Muscari, A., Pikija, S., Probstfield, J., Rost, N. S., Thrift, A. G., Vemmos, K., and Kelly, P. J. (2013) Statin therapy and outcome after ischemic stroke: systematic review and meta-analysis of observational studies and randomized trials. Stroke 44, 448-456
11. Ahmed M. H., and Byrne, C. D. (2008) Current treatment of non-alcoholic fatty liver disease. Diabetes Obes. Metab. 11, 188-195
12. Katz, S. (2008) Potential role of statins in the treatment of heart failure. Curr. Atheroscler. Rep. 10, 318-323
13. Palmer, S. C., Craig, J. C., Navaneethan, S. D., Tonelli, M., Pellegrini, F., and Strippoli, G. F. (2012) Benefits and harms of statin therapy for persons with chronic kidney disease: a systematic review and meta-analysis. Ann. Intern. Med. 157, 263-275
14. Upadhyay, A., Earley, A., Lamont, J. L., Haynes, S., Wanner, C., and Balk, E. M. (2012) Lipid-lowering therapy in persons with chronic kidney disease: a systematic review and meta-analysis. Ann. Intern. Med. 157, 251-262
15. Jukema, J. W., Cannon, C. P., de Craen, A. J., Westendorp, R. G., and Trompet, S. (2012) The controversies of statin therapy: weighing the evidence. J. Am. Coll. Cardiol. 60, 875-881
16. Tenenbaum, A., and Fisman, E. Z. (2012) Fibrates are an essential part of modern anti-dyslipidemic arsenal: spotlight on atherogenic dyslipidemia and residual risk reduction. Cardiovasc. Diabetol. 11, 125
17. Colbert, J. D., and Stone, J. A. (2012) Statin use and the risk of incident diabetes mellitus: a review of the literature. Can. J. Cardiol. 28, 581-589
18. Stein, E. A. (2013) Low-density lipoprotein cholesterol reduction by inhibition of PCSK9. Curr. Opin. Lipidol. 24, 510-517
19. Wang, X., Briggs, M. R., Hua, X., Yokoyama, C., Goldstein, J. L., and Brown, M. S. (1993) Nuclear protein that binds sterol regulatory element of low density lipoprotein recpetor promoter. II. Purification and characterization. J. Biol. Chem. 268, 14497-14504 (Pubitemid 23195581)
20. Sakai, J., Rawson, R. B., Espenshade, P. J., Cheng, D., Seegmiller, A. C., Goldstein, J. L., and Brown, M. S. (1998) Molecular identification of the sterol-regulated luminal protease that cleaves SREBPs and controls lipid composition of animal cells. Mol. Cell 2, 505-514 (Pubitemid 128381303)
21. Brown, M. S., and Goldstein, J. L. (1997) The SREBP pathway: regulation of cholesterol metabolism by proteolysis of a membrane-bound transcription factor. Cell 89, 331-340 (Pubitemid 27220877)
22. Cohen, P. T., Brewis, N. D., Hughes, V., and Mann, D. J. (1990) Protein serine/threonine phosphatases: an expanding family. FEBS Lett. 268, 355-359 (Pubitemid 20241342)
23. Janssens, V., Longin, S., and Goris, J. (2008) PP2A holoenzyme assembly: in cauda venenum (the sting is in the tail) Trends Biochem. Sci. 33, 113-121
24. Hernández, M. L., Martínez, M. J., López de Heredia, M., and Ochoa, B. (1997) Protein phosphatase 1 and 2A inhibitors activate acyl-CoA:cholesterol acyltransferase and cholesterol ester formation in isolated rat hepatocytes. Biochim. Biophys. Acta 1349, 233-241 (Pubitemid 28032124)
25. Jefcoate, C. R., Lee, J., Cherradi, N., Takemori, H., and Duan, H. (2011) cAMP stimulation of StAR expression and cholesterol metabolism is modulated by co-expression of labile suppressors of transcription and mRNA turnover. Mol. Cell. Endocrinol. 336, 53-62
26. Jones, P. M., Sayed, S. B., Persaud, S. J., Burns, C. J., Gyles, S., and Whitehouse, B. J. (2000) Cyclic AMP-induced expression of steroidogenic acute regulatory protein is dependent upon phosphoprotein phosphatase activities. J. Mol. Endocrinol. 24, 233-239 (Pubitemid 30187053)
27. Wang, P. Y., Liu, P., Weng, J., Sontag, E., and Anderson, R. G. (2003) A cholesterol-regulated PP2A/HePTP complex with dual specificity ERK1/2 phosphatase activity. EMBO J. 22, 2658-2667 (Pubitemid 36712363)
28. Wang, P. Y., Weng, J., and Anderson, R. G. (2005) OSBP is a cholesterol-regulated scaffolding protein in control of ERK 1/2 activation. Science 307, 1472-1476 (Pubitemid 40321946)
29. Holen, I., Gordon, P. B., and Seglen, P. O. (1993) Inhibition of hepatocytic autophagy by okadaic acid and other protein phosphatase inhibitors. Eur. J. Biochem. 215, 113-122 (Pubitemid 23211132)
30. Shen, L., Hillebrand, A., Wang, D. Q., and Liu, M. (2012) Isolation and primary culture of rat hepatic cells. J. Vis. Exp. 10.3791/3917
31. Seglen, P. O. (1976) Preparation of isolated rat liver cells. Methods Cell Biol. 13, 29-83
32. Matsui, M., Sakurai, F., Elbashir, S., Foster, D. J., Manoharan, M., and Corey, D. R. (2010) Activation of LDL receptor expression by small RNAs complementary to a noncoding transcript that overlaps the LDLR promoter. Chem. Biol. 17, 1344-1355
33. Frey, T., and De Maio, A. (2007) Increased expression of CD14 in macrophages after inhibition of the cholesterol biosynthetic pathway by lovastatin. Mol. Med. 13, 592-604 (Pubitemid 350228720)
34. Lee, J., and Stock, J. (1993) Protein phosphatase 2A catalytic subunit is methyl-esterified at its carboxyl terminus by a novel methyltransferase. J. Biol. Chem. 268, 19192-19195 (Pubitemid 23270686)
35. Rawson, R. B., Zelenski, N. G., Nijhawan, D., Ye, J., Sakai, J., Hasan, M. T., Chang, T. Y., Brown, M. S., and Goldstein, J. L. (1997) Complementation cloning of S2P, a gene encoding a putative metalloprotease reqired for intramembrane cleavage of SREBPs. Mol. Cell 1, 47-57 (Pubitemid 127376392)
36. Pallai, R., Bhaskar, A., Sodi, V., and Rice, L. M. (2012) Ets1 and Elk1 transcription factors regulate cancerous inhibitor of protein phosphatase 2A expression in cervical and endometrial carcinoma cells. Transcription 3, 323-335
37. Kurachi, S., Huo, J. S., Ameri, A., Zhang, K., Yoshizawa, A. C., and Kurachi, K. (2009) An age-related homeostasis mechanism is essential for spontaneous amelioration of hemophilia B Leyden. Proc. Natl. Acad. Sci. U.S.A. 106, 7921-7926
38. Sundqvist, A., Bengoechea-Alonso, M. T., Ye, X., Lukiyanchuk, V., Jin, J., Harper, J. W., and Ericsson, J. (2005) Control of lipid metabolism by phosphorylation-dependent degradation of the SREBP family of transcription factors by SCF(Fbw7). Cell Metab. 1, 379-391 (Pubitemid 43960622)
39. Kotzka, J., Lehr, S., Roth, G., Avci, H., Knebel, B., and Muller-Wieland, D. (2004) Insulin-activated Erk-mitogen-activated protein kinases phosphorylate sterol regulatory element-binding protein-2 at serine residues 432 and 455 in vivo. J. Biol. Chem. 279, 22404-22411 (Pubitemid 38679438)
40. Wong, R. H., and Sul, H. S. (2010) Insulin signaling in fatty acid and fat synthesis: a transcriptional perspective. Curr. Opin. Pharmacol. 10, 684-691
41. Roth, G., Kotzka, J., Kremer, L., Lehr, S., Lohaus, C., Meyer, H. E., Krone, W., and Müller-Wieland, D. (2000) MAP kinases Erk1/2 phosphorylate sterol regulatory element-binding protein (SREBP)-1a at serine 117 in vitro. J. Biol. Chem. 275, 33302-33307
42. Lu, M., and Shyy, J. Y. (2006) Sterol regulatory element-binding protein 1 is negatively modulated by PKA phosphorylation. Am. J. Physiol. Cell Physiol. 290, C1477-C1486 (Pubitemid 43830787)
43. Punga, T., Bengoechea-Alonso, M. T., and Ericsson, J. (2006) Phosphorylation and ubiquitination of the transcription factor sterol regulatory element-binding protein-1 in response to DNA binding. J. Biol. Chem. 281, 25278-25286 (Pubitemid 44401915)
44. Bengoechea-Alonso, M. T., and Ericsson, J. (2006) Cdk1/cyclin B-mediated phosphorylation stabilizes SREBP1 during mitosis. Cell Cycle 5, 1708-1718 (Pubitemid 44285259)
45. Kotzka, J., Knebel, B., Haas, J., Kremer, L., Jacob, S., Hartwig, S., Nitzgen, U., and Muller-Wieland, D. (2012) Preventing phosphorylation of sterol regulatory element-binding protein 1a by MAP-kinases protects mice from fatty liver and visceral obesity. PLoS One 7, e32609
46. Kotzka, J., Knebel, B., Avci, H., Jacob, S., Nitzgen, U., Jockenhovel, F., Heeren, J., Haas, J., and Muller-Wieland, D. (2010) Phosphorylation of sterol regulatory element-binding protein (SREBP)-1a links growth hormone action to lipid metabolism in hepatocytes. Atherosclerosis 213, 156-165
47. Yoon, Y. S., Seo, W. Y., Lee, M. W., Kim, S. T., and Koo, S. H. (2009) Salt-inducible kinase regulates hepatic lipogenesis by controlling SREBP-1c phosphorylation. J. Biol. Chem. 284, 10446-10452
48. Li, Y., Xu, S., Mihaylova, M. M., Zheng, B., Hou, X., Jiang, B., Park, O., Luo, Z., Lefai, E., Shyy, J. Y., Gao, B., Wierzbicki, M., Verbeuren, T. J., Shaw, R. J., Cohen, R. A., and Zang, M. (2011) AMPK phosphorylates and inhibits SREBP activity to attenuate hepatic steatosis and atherosclerosis in diet-induced insulin-resistant mice. Cell Metab. 13, 376-388
49. Goldstein, J. L., and Brown, M. S. (1990) Regulation of the mevalonate pathway. Nature 343, 425-430
50. Nagoshi, E., and Yoneda, Y. (2001) Dimerization of sterol regulatory element-binding protein 2 via the helix-loop-helix-leucine zipper domain is a prerequisite for its nuclear localization mediated by importin β. Mol. Cell. Biol. 21, 2779-2789 (Pubitemid 32244922)
51. Datta, S., and Osborne, T. F. (2005) Activation domains from both monomers contribute to transcriptional stimulation by sterol regulatory ele-ment- binding protein dimers. J. Biol. Chem. 280, 3338-3345 (Pubitemid 40223796)
52. Magana, M. M., and Osborne, T. F. (1996) Two tandem binding sites for sterol regulatory element binding proteins are required for sterol regulation of fatty-acid synthase promoter. J. Biol. Chem. 271, 32689-32694 (Pubitemid 27008692)
53. Magana, M. M., Koo, S. H., Towle, H. C., and Osborne, T. F. (2000) Different sterol regulatory element-binding protein-1 isoforms utilize distinct co-regulatory factors to activate the promoter for fatty acid synthase. J. Biol. Chem. 275, 4726-4733 (Pubitemid 30108861)
54. Bennett, M. K., Seo, Y. K., Datta, S., Shin, D. J., and Osborne, T. F. (2008) Selective binding of sterol regulatory element-binding protein isoforms and co-regulatory proteins to promoters for lipid metabolic genes in liver. J. Biol. Chem. 283, 15628-15637
55. Lloyd, D. B., and Thompson, J. F. (1995) Transcriptional modulators affect in vivo protein binding to the low density lipoprotein receptor and 3-hydroxy-3-methylglutaryl coenzyme A reductase promoters. J. Biol. Chem. 270, 25812-25818
56. Pak, Y. K. (1996) Serum response element-like sequences of the human low density lipoprotein receptor promoter: possible regulation sites for sterol-independent transcriptional activation. Biochem. Mol. Biol. Int. 38, 31-36
57. Li, C., Kraemer, F. B., Ahlborn, T. E., and Liu, J. (1999) Induction of low density lipoprotein receptor (LDLR) transcription by oncostatin M is mediated by the extracellular signal-regulated kinase signaling pathway and the repeat 3 element of the LDLR promoter. J. Biol. Chem. 274, 6747-6753 (Pubitemid 29111097)
58. Iizuka, K., and Horikawa, Y. (2008) ChREBP: a glucose-activated transcription factor involved in the development of metabolic syndrome. Endocr. J. 55, 617-624
59. Khoo, M. C., Oliveira, F. M., and Cheng, L. (2013) Understanding the metabolic syndrome: a modeling perspective. IEEE Rev. Biomed. Eng. 6, 143-155
60. Ni, Y. G., Wang, N., Cao, D. J., Sachan, N., Morris, D. J., Gerard, R. D., Kuro-O, M., Rothermel, B. A., and Hill, J. A. (2007) FoxO transcription factors activate Akt and attenuate insulin signaling in heart by inhibiting protein phosphatases. Proc. Natl. Acad. Sci. U.S.A. 104, 20517-20522
61. DeGrande, S. T., Little, S. C., Nixon, D. J., Wright, P., Snyder, J., Dun, W., Murphy, N., Kilic, A., Higgins, R., Binkley, P. F., Boyden, P. A., Carnes, C. A., Anderson, M. E., Hund, T. J., and Mohler, P. J. (2013) Molecular mechanisms underlying cardiac protein phosphatase 2A regulation in heart. J. Biol. Chem. 288, 1032-1046
62. Sablina, A. A., Hector, M., Colpaert, N., and Hahn, W. C. (2010) Identification of PP2A complexes and pathways involved in cell transformation. Cancer Res. 70, 10474-10484
63. Rodgers, J. T., Vogel, R. O., and Puigserver, P. (2011) Clk2 and B56β mediate insulin-regulated assembly of the PP2A phosphatase holoenzyme complex on Akt. Mol. Cell 41, 471-479
64. Li, Y., Wei, H., Hsieh, T. C., and Pallas, D. C. (2008) Cdc55p-mediated E4orf4 growth inhibition in Saccharomyces cerevisiae is mediated only in part via the catalytic subunit of protein phosphatase 2A. J. Virol. 82, 3612-3623 (Pubitemid 351429937)
65. Zhang, Z., Mui, M. Z., Chan, F., Roopchand, D. E., Marcellus, R. C., Blanchette, P., Li, S., Berghuis, A. M., and Branton, P. E. (2011) Genetic analysis of B55α/Cdc55 protein phosphatase 2A subunits: association with the adenovirus E4orf4 protein. J. Virol. 85, 286-295
66. Mui, M. Z., Roopchand, D. E., Gentry, M. S., Hallberg, R. L., Vogel, J., and Branton, P. E. (2010) Adenovirus protein E4orf4 induces premature AP-CCdc20 activation in Saccharomyces cerevisiae by a protein phosphatase 2A-dependent mechanism. J. Virol. 84, 4798-4809