Abstract
Adipocyte differentiation is thought to involve sequential induction of the transcription factors C/EBPbeta, peroxisome proliferator-activated receptor gamma (PPARgamma), and C/EBPalpha. C/EBPalpha expression is both necessary and sufficient for adipocyte differentiation. Here we report that ectopic expression of either C/EBPalpha or C/EBPbeta induces PPARgamma expression and adipogenesis and that retinoic acid (RA) completely inhibits adipogenesis by either form of C/EBP. In studies of normal preadipocytes, RA does not prevent C/EBPbeta induction but blocks induction of PPARgamma, C/EBPalpha, and adipogenesis. In transient transfection studies, liganded RA receptor (RAR) specifically blocks transcriptional activation by either C/EBPalpha or C/EBPbeta. These results strongly suggest that C/EBPalpha substitutes for C/EBPbeta to induce adipocyte differentiation and that liganded RAR inhibits adipogenesis by blocking C/EBPbeta-mediated induction of downstream genes.
Full Text
The Full Text of this article is available as a PDF (759.6 KB).
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Akira S., Isshiki H., Sugita T., Tanabe O., Kinoshita S., Nishio Y., Nakajima T., Hirano T., Kishimoto T. A nuclear factor for IL-6 expression (NF-IL6) is a member of a C/EBP family. EMBO J. 1990 Jun;9(6):1897–1906. doi: 10.1002/j.1460-2075.1990.tb08316.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Avitahl N., Calame K. The C/EBP family of proteins distorts DNA upon binding but does not introduce a large directed bend. J Biol Chem. 1994 Sep 23;269(38):23553–23562. [PubMed] [Google Scholar]
- Brent G. A., Harney J. W., Chen Y., Warne R. L., Moore D. D., Larsen P. R. Mutations of the rat growth hormone promoter which increase and decrease response to thyroid hormone define a consensus thyroid hormone response element. Mol Endocrinol. 1989 Dec;3(12):1996–2004. doi: 10.1210/mend-3-12-1996. [DOI] [PubMed] [Google Scholar]
- Bugge T. H., Pohl J., Lonnoy O., Stunnenberg H. G. RXR alpha, a promiscuous partner of retinoic acid and thyroid hormone receptors. EMBO J. 1992 Apr;11(4):1409–1418. doi: 10.1002/j.1460-2075.1992.tb05186.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Caldenhoven E., Liden J., Wissink S., Van de Stolpe A., Raaijmakers J., Koenderman L., Okret S., Gustafsson J. A., Van der Saag P. T. Negative cross-talk between RelA and the glucocorticoid receptor: a possible mechanism for the antiinflammatory action of glucocorticoids. Mol Endocrinol. 1995 Apr;9(4):401–412. doi: 10.1210/mend.9.4.7659084. [DOI] [PubMed] [Google Scholar]
- Cao Z., Umek R. M., McKnight S. L. Regulated expression of three C/EBP isoforms during adipose conversion of 3T3-L1 cells. Genes Dev. 1991 Sep;5(9):1538–1552. doi: 10.1101/gad.5.9.1538. [DOI] [PubMed] [Google Scholar]
- Cavaillès V., Dauvois S., L'Horset F., Lopez G., Hoare S., Kushner P. J., Parker M. G. Nuclear factor RIP140 modulates transcriptional activation by the estrogen receptor. EMBO J. 1995 Aug 1;14(15):3741–3751. doi: 10.1002/j.1460-2075.1995.tb00044.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Chakravarti D., LaMorte V. J., Nelson M. C., Nakajima T., Schulman I. G., Juguilon H., Montminy M., Evans R. M. Role of CBP/P300 in nuclear receptor signalling. Nature. 1996 Sep 5;383(6595):99–103. doi: 10.1038/383099a0. [DOI] [PubMed] [Google Scholar]
- Chawla A., Lazar M. A. Induction of Rev-ErbA alpha, an orphan receptor encoded on the opposite strand of the alpha-thyroid hormone receptor gene, during adipocyte differentiation. J Biol Chem. 1993 Aug 5;268(22):16265–16269. [PubMed] [Google Scholar]
- Chawla A., Lazar M. A. Peroxisome proliferator and retinoid signaling pathways co-regulate preadipocyte phenotype and survival. Proc Natl Acad Sci U S A. 1994 Mar 1;91(5):1786–1790. doi: 10.1073/pnas.91.5.1786. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Chawla A., Schwarz E. J., Dimaculangan D. D., Lazar M. A. Peroxisome proliferator-activated receptor (PPAR) gamma: adipose-predominant expression and induction early in adipocyte differentiation. Endocrinology. 1994 Aug;135(2):798–800. doi: 10.1210/endo.135.2.8033830. [DOI] [PubMed] [Google Scholar]
- Chen J. D., Evans R. M. A transcriptional co-repressor that interacts with nuclear hormone receptors. Nature. 1995 Oct 5;377(6548):454–457. doi: 10.1038/377454a0. [DOI] [PubMed] [Google Scholar]
- Christy R. J., Kaestner K. H., Geiman D. E., Lane M. D. CCAAT/enhancer binding protein gene promoter: binding of nuclear factors during differentiation of 3T3-L1 preadipocytes. Proc Natl Acad Sci U S A. 1991 Mar 15;88(6):2593–2597. doi: 10.1073/pnas.88.6.2593. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Christy R. J., Yang V. W., Ntambi J. M., Geiman D. E., Landschulz W. H., Friedman A. D., Nakabeppu Y., Kelly T. J., Lane M. D. Differentiation-induced gene expression in 3T3-L1 preadipocytes: CCAAT/enhancer binding protein interacts with and activates the promoters of two adipocyte-specific genes. Genes Dev. 1989 Sep;3(9):1323–1335. doi: 10.1101/gad.3.9.1323. [DOI] [PubMed] [Google Scholar]
- Damm K., Heyman R. A., Umesono K., Evans R. M. Functional inhibition of retinoic acid response by dominant negative retinoic acid receptor mutants. Proc Natl Acad Sci U S A. 1993 Apr 1;90(7):2989–2993. doi: 10.1073/pnas.90.7.2989. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Danielian P. S., White R., Lees J. A., Parker M. G. Identification of a conserved region required for hormone dependent transcriptional activation by steroid hormone receptors. EMBO J. 1992 Mar;11(3):1025–1033. doi: 10.1002/j.1460-2075.1992.tb05141.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Davis K. D., Berrodin T. J., Stelmach J. E., Winkler J. D., Lazar M. A. Endogenous retinoid X receptors can function as hormone receptors in pituitary cells. Mol Cell Biol. 1994 Nov;14(11):7105–7110. doi: 10.1128/mcb.14.11.7105. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Descombes P., Schibler U. A liver-enriched transcriptional activator protein, LAP, and a transcriptional inhibitory protein, LIP, are translated from the same mRNA. Cell. 1991 Nov 1;67(3):569–579. doi: 10.1016/0092-8674(91)90531-3. [DOI] [PubMed] [Google Scholar]
- Dimaculangan D. D., Chawla A., Boak A., Kagan H. M., Lazar M. A. Retinoic acid prevents downregulation of ras recision gene/lysyl oxidase early in adipocyte differentiation. Differentiation. 1994 Nov;58(1):47–52. doi: 10.1046/j.1432-0436.1994.5810047.x. [DOI] [PubMed] [Google Scholar]
- Durand B., Saunders M., Gaudon C., Roy B., Losson R., Chambon P. Activation function 2 (AF-2) of retinoic acid receptor and 9-cis retinoic acid receptor: presence of a conserved autonomous constitutive activating domain and influence of the nature of the response element on AF-2 activity. EMBO J. 1994 Nov 15;13(22):5370–5382. doi: 10.1002/j.1460-2075.1994.tb06872.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Forman B. M., Tontonoz P., Chen J., Brun R. P., Spiegelman B. M., Evans R. M. 15-Deoxy-delta 12, 14-prostaglandin J2 is a ligand for the adipocyte determination factor PPAR gamma. Cell. 1995 Dec 1;83(5):803–812. doi: 10.1016/0092-8674(95)90193-0. [DOI] [PubMed] [Google Scholar]
- Freytag S. O., Paielli D. L., Gilbert J. D. Ectopic expression of the CCAAT/enhancer-binding protein alpha promotes the adipogenic program in a variety of mouse fibroblastic cells. Genes Dev. 1994 Jul 15;8(14):1654–1663. doi: 10.1101/gad.8.14.1654. [DOI] [PubMed] [Google Scholar]
- Halachmi S., Marden E., Martin G., MacKay H., Abbondanza C., Brown M. Estrogen receptor-associated proteins: possible mediators of hormone-induced transcription. Science. 1994 Jun 3;264(5164):1455–1458. doi: 10.1126/science.8197458. [DOI] [PubMed] [Google Scholar]
- Hanstein B., Eckner R., DiRenzo J., Halachmi S., Liu H., Searcy B., Kurokawa R., Brown M. p300 is a component of an estrogen receptor coactivator complex. Proc Natl Acad Sci U S A. 1996 Oct 15;93(21):11540–11545. doi: 10.1073/pnas.93.21.11540. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Imakado S., Bickenbach J. R., Bundman D. S., Rothnagel J. A., Attar P. S., Wang X. J., Walczak V. R., Wisniewski S., Pote J., Gordon J. S. Targeting expression of a dominant-negative retinoic acid receptor mutant in the epidermis of transgenic mice results in loss of barrier function. Genes Dev. 1995 Feb 1;9(3):317–329. doi: 10.1101/gad.9.3.317. [DOI] [PubMed] [Google Scholar]
- Janknecht R., Hunter T. Transcription. A growing coactivator network. Nature. 1996 Sep 5;383(6595):22–23. doi: 10.1038/383022a0. [DOI] [PubMed] [Google Scholar]
- Kamei Y., Kawada T., Kazuki R., Sugimoto E. Retinoic acid receptor gamma 2 gene expression is up-regulated by retinoic acid in 3T3-L1 preadipocytes. Biochem J. 1993 Aug 1;293(Pt 3):807–812. doi: 10.1042/bj2930807. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kamei Y., Xu L., Heinzel T., Torchia J., Kurokawa R., Gloss B., Lin S. C., Heyman R. A., Rose D. W., Glass C. K. A CBP integrator complex mediates transcriptional activation and AP-1 inhibition by nuclear receptors. Cell. 1996 May 3;85(3):403–414. doi: 10.1016/s0092-8674(00)81118-6. [DOI] [PubMed] [Google Scholar]
- Kato G. J., Barrett J., Villa-Garcia M., Dang C. V. An amino-terminal c-myc domain required for neoplastic transformation activates transcription. Mol Cell Biol. 1990 Nov;10(11):5914–5920. doi: 10.1128/mcb.10.11.5914. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kletzien R. F., Clarke S. D., Ulrich R. G. Enhancement of adipocyte differentiation by an insulin-sensitizing agent. Mol Pharmacol. 1992 Feb;41(2):393–398. [PubMed] [Google Scholar]
- Kliewer S. A., Lenhard J. M., Willson T. M., Patel I., Morris D. C., Lehmann J. M. A prostaglandin J2 metabolite binds peroxisome proliferator-activated receptor gamma and promotes adipocyte differentiation. Cell. 1995 Dec 1;83(5):813–819. doi: 10.1016/0092-8674(95)90194-9. [DOI] [PubMed] [Google Scholar]
- Kliewer S. A., Umesono K., Mangelsdorf D. J., Evans R. M. Retinoid X receptor interacts with nuclear receptors in retinoic acid, thyroid hormone and vitamin D3 signalling. Nature. 1992 Jan 30;355(6359):446–449. doi: 10.1038/355446a0. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kliewer S. A., Umesono K., Noonan D. J., Heyman R. A., Evans R. M. Convergence of 9-cis retinoic acid and peroxisome proliferator signalling pathways through heterodimer formation of their receptors. Nature. 1992 Aug 27;358(6389):771–774. doi: 10.1038/358771a0. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kuri-Harcuch W. Differentiation of 3T3-F442A cells into adipocytes is inhibited by retinoic acid. Differentiation. 1982;23(2):164–169. doi: 10.1111/j.1432-0436.1982.tb01279.x. [DOI] [PubMed] [Google Scholar]
- Kurokawa R., DiRenzo J., Boehm M., Sugarman J., Gloss B., Rosenfeld M. G., Heyman R. A., Glass C. K. Regulation of retinoid signalling by receptor polarity and allosteric control of ligand binding. Nature. 1994 Oct 6;371(6497):528–531. doi: 10.1038/371528a0. [DOI] [PubMed] [Google Scholar]
- Le Douarin B., Zechel C., Garnier J. M., Lutz Y., Tora L., Pierrat P., Heery D., Gronemeyer H., Chambon P., Losson R. The N-terminal part of TIF1, a putative mediator of the ligand-dependent activation function (AF-2) of nuclear receptors, is fused to B-raf in the oncogenic protein T18. EMBO J. 1995 May 1;14(9):2020–2033. doi: 10.1002/j.1460-2075.1995.tb07194.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lee J. W., Ryan F., Swaffield J. C., Johnston S. A., Moore D. D. Interaction of thyroid-hormone receptor with a conserved transcriptional mediator. Nature. 1995 Mar 2;374(6517):91–94. doi: 10.1038/374091a0. [DOI] [PubMed] [Google Scholar]
- Lehmann J. M., Moore L. B., Smith-Oliver T. A., Wilkison W. O., Willson T. M., Kliewer S. A. An antidiabetic thiazolidinedione is a high affinity ligand for peroxisome proliferator-activated receptor gamma (PPAR gamma). J Biol Chem. 1995 Jun 2;270(22):12953–12956. doi: 10.1074/jbc.270.22.12953. [DOI] [PubMed] [Google Scholar]
- Lehmann J. M., Zhang X. K., Pfahl M. RAR gamma 2 expression is regulated through a retinoic acid response element embedded in Sp1 sites. Mol Cell Biol. 1992 Jul;12(7):2976–2985. doi: 10.1128/mcb.12.7.2976. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lillie J. W., Green M. R. Transcription activation by the adenovirus E1a protein. Nature. 1989 Mar 2;338(6210):39–44. doi: 10.1038/338039a0. [DOI] [PubMed] [Google Scholar]
- Lin F. T., Lane M. D. Antisense CCAAT/enhancer-binding protein RNA suppresses coordinate gene expression and triglyceride accumulation during differentiation of 3T3-L1 preadipocytes. Genes Dev. 1992 Apr;6(4):533–544. doi: 10.1101/gad.6.4.533. [DOI] [PubMed] [Google Scholar]
- Lin F. T., Lane M. D. CCAAT/enhancer binding protein alpha is sufficient to initiate the 3T3-L1 adipocyte differentiation program. Proc Natl Acad Sci U S A. 1994 Sep 13;91(19):8757–8761. doi: 10.1073/pnas.91.19.8757. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lin F. T., MacDougald O. A., Diehl A. M., Lane M. D. A 30-kDa alternative translation product of the CCAAT/enhancer binding protein alpha message: transcriptional activator lacking antimitotic activity. Proc Natl Acad Sci U S A. 1993 Oct 15;90(20):9606–9610. doi: 10.1073/pnas.90.20.9606. [DOI] [PMC free article] [PubMed] [Google Scholar]
- MacDougald O. A., Lane M. D. Transcriptional regulation of gene expression during adipocyte differentiation. Annu Rev Biochem. 1995;64:345–373. doi: 10.1146/annurev.bi.64.070195.002021. [DOI] [PubMed] [Google Scholar]
- Miller A. D., Rosman G. J. Improved retroviral vectors for gene transfer and expression. Biotechniques. 1989 Oct;7(9):980-2, 984-6, 989-90. [PMC free article] [PubMed] [Google Scholar]
- Nerlov C., Ziff E. B. CCAAT/enhancer binding protein-alpha amino acid motifs with dual TBP and TFIIB binding ability co-operate to activate transcription in both yeast and mammalian cells. EMBO J. 1995 Sep 1;14(17):4318–4328. doi: 10.1002/j.1460-2075.1995.tb00106.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Nerlov C., Ziff E. B. Three levels of functional interaction determine the activity of CCAAT/enhancer binding protein-alpha on the serum albumin promoter. Genes Dev. 1994 Feb 1;8(3):350–362. doi: 10.1101/gad.8.3.350. [DOI] [PubMed] [Google Scholar]
- Osada S., Yamamoto H., Nishihara T., Imagawa M. DNA binding specificity of the CCAAT/enhancer-binding protein transcription factor family. J Biol Chem. 1996 Feb 16;271(7):3891–3896. doi: 10.1074/jbc.271.7.3891. [DOI] [PubMed] [Google Scholar]
- Ossipow V., Descombes P., Schibler U. CCAAT/enhancer-binding protein mRNA is translated into multiple proteins with different transcription activation potentials. Proc Natl Acad Sci U S A. 1993 Sep 1;90(17):8219–8223. doi: 10.1073/pnas.90.17.8219. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Oñate S. A., Tsai S. Y., Tsai M. J., O'Malley B. W. Sequence and characterization of a coactivator for the steroid hormone receptor superfamily. Science. 1995 Nov 24;270(5240):1354–1357. doi: 10.1126/science.270.5240.1354. [DOI] [PubMed] [Google Scholar]
- Pfahl M. Nuclear receptor/AP-1 interaction. Endocr Rev. 1993 Oct;14(5):651–658. doi: 10.1210/edrv-14-5-651. [DOI] [PubMed] [Google Scholar]
- Pizzorno M. C., Mullen M. A., Chang Y. N., Hayward G. S. The functionally active IE2 immediate-early regulatory protein of human cytomegalovirus is an 80-kilodalton polypeptide that contains two distinct activator domains and a duplicated nuclear localization signal. J Virol. 1991 Jul;65(7):3839–3852. doi: 10.1128/jvi.65.7.3839-3852.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Ray A., Prefontaine K. E. Physical association and functional antagonism between the p65 subunit of transcription factor NF-kappa B and the glucocorticoid receptor. Proc Natl Acad Sci U S A. 1994 Jan 18;91(2):752–756. doi: 10.1073/pnas.91.2.752. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Saatcioglu F., Claret F. X., Karin M. Negative transcriptional regulation by nuclear receptors. Semin Cancer Biol. 1994 Oct;5(5):347–359. [PubMed] [Google Scholar]
- Sandouk T., Reda D., Hofmann C. Antidiabetic agent pioglitazone enhances adipocyte differentiation of 3T3-F442A cells. Am J Physiol. 1993 Jun;264(6 Pt 1):C1600–C1608. doi: 10.1152/ajpcell.1993.264.6.C1600. [DOI] [PubMed] [Google Scholar]
- Scheinman R. I., Gualberto A., Jewell C. M., Cidlowski J. A., Baldwin A. S., Jr Characterization of mechanisms involved in transrepression of NF-kappa B by activated glucocorticoid receptors. Mol Cell Biol. 1995 Feb;15(2):943–953. doi: 10.1128/mcb.15.2.943. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Stein B., Yang M. X. Repression of the interleukin-6 promoter by estrogen receptor is mediated by NF-kappa B and C/EBP beta. Mol Cell Biol. 1995 Sep;15(9):4971–4979. doi: 10.1128/mcb.15.9.4971. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Stone R. L., Bernlohr D. A. The molecular basis for inhibition of adipose conversion of murine 3T3-L1 cells by retinoic acid. Differentiation. 1990 Nov;45(2):119–127. doi: 10.1111/j.1432-0436.1990.tb00465.x. [DOI] [PubMed] [Google Scholar]
- Tontonoz P., Hu E., Devine J., Beale E. G., Spiegelman B. M. PPAR gamma 2 regulates adipose expression of the phosphoenolpyruvate carboxykinase gene. Mol Cell Biol. 1995 Jan;15(1):351–357. doi: 10.1128/mcb.15.1.351. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Tontonoz P., Hu E., Graves R. A., Budavari A. I., Spiegelman B. M. mPPAR gamma 2: tissue-specific regulator of an adipocyte enhancer. Genes Dev. 1994 May 15;8(10):1224–1234. doi: 10.1101/gad.8.10.1224. [DOI] [PubMed] [Google Scholar]
- Tontonoz P., Hu E., Spiegelman B. M. Stimulation of adipogenesis in fibroblasts by PPAR gamma 2, a lipid-activated transcription factor. Cell. 1994 Dec 30;79(7):1147–1156. doi: 10.1016/0092-8674(94)90006-x. [DOI] [PubMed] [Google Scholar]
- Tsai S., Bartelmez S., Heyman R., Damm K., Evans R., Collins S. J. A mutated retinoic acid receptor-alpha exhibiting dominant-negative activity alters the lineage development of a multipotent hematopoietic cell line. Genes Dev. 1992 Dec;6(12A):2258–2269. doi: 10.1101/gad.6.12a.2258. [DOI] [PubMed] [Google Scholar]
- Vasseur-Cognet M., Lane M. D. CCAAT/enhancer binding protein alpha (C/EBP alpha) undifferentiated protein: a developmentally regulated nuclear protein that binds to the C/EBP alpha gene promoter. Proc Natl Acad Sci U S A. 1993 Aug 1;90(15):7312–7316. doi: 10.1073/pnas.90.15.7312. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Wang N. D., Finegold M. J., Bradley A., Ou C. N., Abdelsayed S. V., Wilde M. D., Taylor L. R., Wilson D. R., Darlington G. J. Impaired energy homeostasis in C/EBP alpha knockout mice. Science. 1995 Aug 25;269(5227):1108–1112. doi: 10.1126/science.7652557. [DOI] [PubMed] [Google Scholar]
- Williams S. C., Baer M., Dillner A. J., Johnson P. F. CRP2 (C/EBP beta) contains a bipartite regulatory domain that controls transcriptional activation, DNA binding and cell specificity. EMBO J. 1995 Jul 3;14(13):3170–3183. doi: 10.1002/j.1460-2075.1995.tb07319.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Wu Z., Bucher N. L., Farmer S. R. Induction of peroxisome proliferator-activated receptor gamma during the conversion of 3T3 fibroblasts into adipocytes is mediated by C/EBPbeta, C/EBPdelta, and glucocorticoids. Mol Cell Biol. 1996 Aug;16(8):4128–4136. doi: 10.1128/mcb.16.8.4128. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Wu Z., Xie Y., Bucher N. L., Farmer S. R. Conditional ectopic expression of C/EBP beta in NIH-3T3 cells induces PPAR gamma and stimulates adipogenesis. Genes Dev. 1995 Oct 1;9(19):2350–2363. doi: 10.1101/gad.9.19.2350. [DOI] [PubMed] [Google Scholar]
- Xue J. C., Schwarz E. J., Chawla A., Lazar M. A. Distinct stages in adipogenesis revealed by retinoid inhibition of differentiation after induction of PPARgamma. Mol Cell Biol. 1996 Apr;16(4):1567–1575. doi: 10.1128/mcb.16.4.1567. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Yeh W. C., Cao Z., Classon M., McKnight S. L. Cascade regulation of terminal adipocyte differentiation by three members of the C/EBP family of leucine zipper proteins. Genes Dev. 1995 Jan 15;9(2):168–181. doi: 10.1101/gad.9.2.168. [DOI] [PubMed] [Google Scholar]
- Yu K., Bayona W., Kallen C. B., Harding H. P., Ravera C. P., McMahon G., Brown M., Lazar M. A. Differential activation of peroxisome proliferator-activated receptors by eicosanoids. J Biol Chem. 1995 Oct 13;270(41):23975–23983. doi: 10.1074/jbc.270.41.23975. [DOI] [PubMed] [Google Scholar]
- Yu V. C., Delsert C., Andersen B., Holloway J. M., Devary O. V., När A. M., Kim S. Y., Boutin J. M., Glass C. K., Rosenfeld M. G. RXR beta: a coregulator that enhances binding of retinoic acid, thyroid hormone, and vitamin D receptors to their cognate response elements. Cell. 1991 Dec 20;67(6):1251–1266. doi: 10.1016/0092-8674(91)90301-e. [DOI] [PubMed] [Google Scholar]
- Zhu Y., Qi C., Korenberg J. R., Chen X. N., Noya D., Rao M. S., Reddy J. K. Structural organization of mouse peroxisome proliferator-activated receptor gamma (mPPAR gamma) gene: alternative promoter use and different splicing yield two mPPAR gamma isoforms. Proc Natl Acad Sci U S A. 1995 Aug 15;92(17):7921–7925. doi: 10.1073/pnas.92.17.7921. [DOI] [PMC free article] [PubMed] [Google Scholar]