Journal of Life Science (생명과학회지)

Korean Society of Life Science (한국생명과학회)
권호 표지
DOI QR코드

DOI QR Code

Expressional Regulation of Replication Factor C in Adipocyte Differentiation

지방세포분화에서의 replication factor C 단백질의 발현조절

  • Cho, Hyun-Kook (Department of Molecular Biology, Pusan National University) ;
  • Kim, Hye-Young (Department of Molecular Biology, Pusan National University) ;
  • Yu, Hyun-Jeong (Department of Molecular Biology, Pusan National University) ;
  • Cheong, Jae-Hun (Department of Molecular Biology, Pusan National University)
  • 조현국 (부산대학교 분자생물학과) ;
  • 김혜영 (부산대학교 분자생물학과) ;
  • 유현정 (부산대학교 분자생물학과) ;
  • 정재훈 (부산대학교 분자생물학과)
  • Received : 2010.12.14
  • Accepted : 2010.12.15
  • Published : 2011.02.28
Download PDF
⟨ Previous Next ⟩

Abstract

Adipocyte differentiation is an ordered multistep process requiring the sequential activation of several groups of adipogenic transcription factors, including CCAAT/enhancer-binding protein-$\alpha$ and peroxisome proliferator-activated receptor-$\gamma$, and coactivators. In previous reports, we identified that replication factor C 140 (RFC140) protein played a critical role in regulating adipocyte differentiation as a coactivator. Here, we show expressional regulation of RFC140 and small RFC subunit, RFC38, following characterization of gene promoter of RFC140 and RFC38. In addition, RFC140 increases PPAR$\gamma$-mediated gene activation, resulting from direct protein-protein interaction of RFC140 and PPAR$\gamma$. Taken together, these findings demonstrate that the regulated expression of RFC140 and RFC38 by specific adipocyte transcription factors is required for the adipocyte differentiation process.

지방세포 분화 과정 중에 key regulator로서 기능을 하는 여러 전사조절인자(PPAR$\gamma$, C/EBP$\alpha$, SREBP, LXR)가 동정되었고, 주로 DNA 복제나 DNA 수선 단계에서 중요한 역할을 한다고 밝혀진 복제 조절인자인 RFC140이 지방세포 분화에도 중요한 인자임이 밝혀졌다. 이 연구에서 우리는 RFC140과 RFC38에 대한 발현조절을 확인하였으며, RFC140이 PPAR$\gamma$와의 단백질-단백질 결합을 통하여 PPAR$\gamma$에 의해 조절되는 유전자의 발현을 증가시킴을 확인하였다. 이러한 결과들은 특이적인 지방세포 전사인자에 의해 발현이 조절되는 RFC140과 RFC38이 지방세포의 분화과정에 필수적임을 제시한다.

Keywords

References

  1. Altiok, S., M. Xu, and B. M. Spiegelman. 1997. $PPAR{\gamma}$ induces cell cycle withdrawal: inhibition of E2F/DP DNA-binding activity via down-regulation of PP2A. Genes Dev. 11, 1987-1998. https://doi.org/10.1101/gad.11.15.1987
  2. Altschul, S. F., T. L. Madden, A. A. Schaffer, J. Zhang, Z. Zhang, W. Miller, and D. J. Lipman. 1997. Gapped BLAST and PSI-BLAST: a new generation of protein database search programs. Nucleic Acids Res. 25, 3389-402. https://doi.org/10.1093/nar/25.17.3389
  3. Brun, R. P., J. B. Kim, E. Hu, and B. M. Spiegelman. 1997. Peroxisome proliferator-activated receptor gamma and the control of adipogenesis. Curr. Opin. Lipidol. 8, 212-218. https://doi.org/10.1097/00041433-199708000-00004
  4. Cao, Z., R. M. Umek, and S. L. McKnight. 1991. Regulated expression of three C/EBP isoforms during adipose conversion of 3T3-L1 cells. Genes Dev. 5, 1538-1552. https://doi.org/10.1101/gad.5.9.1538
  5. Clarkson, R. W., C. M. Chen, S. Harrison, C. Wells, G. E. Muscat, and M. J. Waters. 1995. Early responses of trans-activating factors to growth hormone in preadipocytes: differential regulation of CCAAT enhancer-binding protein-beta (C/EBP beta) and C/EBPdelta. Mol. Endocrinol. 9, 108-120. https://doi.org/10.1210/me.9.1.108
  6. Dani, C., A. G. Smith, S. Dessolin, P. Leroy, L. Staccini, P. Villageois, C. Darimont, and G. Ailhaud. 1997. Differentiation of embryonic stem cells into adipocytes in vitro. J. Cell Sci. 110, 1279-1285.
  7. DePamphilis, M. L. 1993. Eukaryotic DNA replication: anatomy of an origin. Annu. Rev. Biochem. 62, 29-63. https://doi.org/10.1146/annurev.bi.62.070193.000333
  8. Ferre, P. 2004. The biology of peroxisome proliferator-activated receptors: relationship with lipid metabolism and insulin sensitivity. Diabetes 53, 43-50. https://doi.org/10.2337/diabetes.53.2007.S43
  9. Guerra, C., P. Navarro, A. M. Valverde, M. Arribas, J. Bruning, L. P. Kozak, C. R. Kahn, and M. Benito. 2001. Brown adipose tissue-specific insulin receptor knockout shows diabetic phenotype without insulin resistance. J. Clin. Invest. 108, 1205-1213. https://doi.org/10.1172/JCI13103
  10. Hong, S., S. J. Park, H. J. Kong, J. D. Shuman, and J. Cheong. 2001. Functional interaction of bZIP proteins and the large subunit of replication factor C in liver and adipose cells. J. Biol. Chem. 276, 28098-28105. https://doi.org/10.1074/jbc.M010912200
  11. Iakova, P., S. S. Awad, and N. A. Timchenko. 2003. Aging reduces proliferative capacities of liver by switching pathways of $C/EBP{\alpha}$ growth arrest. Cell 113, 495-506. https://doi.org/10.1016/S0092-8674(03)00318-0
  12. Kolpashchikov, D. M., P. Hughes, A. Favre, G. Baldacci, and O. I. Lavrik. 2001. Localization of the large subunit of replication factor C near the 5’ end of DNA primers. J. Mol. Recognit. 14, 239-244. https://doi.org/10.1002/jmr.538
  13. Lyle, R. E., J. F. Habener, and R. E. Mcgehee. 1996. Antisense oligonucleotides to differentiation-specific element binding protein (DSEB) mRNA inhibit adipocyte differentiation. Biochem. Biophys. Res. Commun. 228, 709-715. https://doi.org/10.1006/bbrc.1996.1721
  14. MacDougald, O. A. and M. D. Lane. 1995. Adipocyte differentiation. When precursors are also regulators. Curr. Biol. 5, 618-621. https://doi.org/10.1016/S0960-9822(95)00125-4
  15. Majka, J. and P. M. Burgers. 2003. Yeast Rad17/Mec3/Ddc1: A sliding clamp for the DNA damage checkpoint. Proc. Natl. Acad. Sci. USA 100, 2249-2254. https://doi.org/10.1073/pnas.0437148100
  16. Maruyama, T., A. Farina, A. Dey, J. Cheong, V. P. Bermudez, T. Tamura, S. Sciortino, J. Shuman, J. Hurwitz, and K. Ozato. 2002. A mammalian bromodomain protein, Brd4, interacts with replication factor C and inhibits progression to S phase. Mol. Cell Biol. 22, 6509-6520. https://doi.org/10.1128/MCB.22.18.6509-6520.2002
  17. McGehee, R. E. Jr. and J. F. Habener. 1995. Differentiation-specific element binding protein (DSEB) binds to a defined element in the promoter of the angiotensinogen gene required for the irreversible induction of gene expression during differentiation of 3T3-L1 adipoblasts to adipocytes. Mol. Endocrinol. 9, 487-501. https://doi.org/10.1210/me.9.4.487
  18. Mossi, R. and U. Hubscher. 1998. Clamping down on clamps and clamp loaders the eukaryotic replication factor C. Eur. J. Biochem. 254, 209-216.
  19. Podust, V. N., N. Tiwari, S. Stephan, and E. Fanning. 1998. Replication factor C disengages from proliferating cell nuclear antigen (PCNA) upon sliding clamp formation, and PCNA itself tethers DNA $polymerase{\delta}$ to DNA. J. Biol. Chem. 273, 31992-31999. https://doi.org/10.1074/jbc.273.48.31992
  20. Prusty, D., B. H. Park, K. E. Davis, and S. R. Farmer. 2002. Activation of MEK/ERK signaling promotes adipogenesis by enhancing peroxisome proliferator-activated receptor gamma $(PPAR{\gamma})$ and $C/EBP{\alpha}$ gene expression during the differentiation of 3T3-L1 preadipocytes. J. Biol. Chem. 277, 46226-46232. https://doi.org/10.1074/jbc.M207776200
  21. Rosen, E. D., P. Sarraf, A. E. Troy, G. Bradwin, K. Moore, D. S. Milstone, B. M. Spiegelman, and R. M. Mortensen. 1999. $PPAR{\gamma}$ is required for the differentiation of adipose tissue in vivo and in vitro. Mol. Cell 4, 611-617. https://doi.org/10.1016/S1097-2765(00)80211-7
  22. Spiegelman, B. M. and J. S. Flier. 1996. Adipogenesis and obesity: rounding out the big picture. Cell 87, 377-389. https://doi.org/10.1016/S0092-8674(00)81359-8
  23. Tamori, Y., J. Masugi, N. Nishino, and M. Kasuga. 2002. Role of Peroxisome Proliferator-Activated Receptor-${\gamma}$ in maintenance of the characteristics of mature 3T3-L1 adipocytes. Diabetes 51, 2045-2055. https://doi.org/10.2337/diabetes.51.7.2045
  24. Tang, Q. Q., T. C. Otto, and M. D. Lane. 2003. Mitotic clonal expansion: a synchronous process required for adipogenesis. Proc. Natl. Acad. Sci. USA 100, 44-49. https://doi.org/10.1073/pnas.0137044100
  25. Tontonoz, P., E. Hu, and B. M. Spiegelman. 1995. Regulation of adipocyte gene expression and differentiation by peroxisome proliferator activated receptor ${\gamma}$. Curr. Opin. Genet. Dev. 5, 571-576. https://doi.org/10.1016/0959-437X(95)80025-5
  26. Yajima, Y., M. Sato, M. Sumida, and S. Kawashima. 2003. Mechanism of adult primitive mesenchymal ST-13 preadipocyte differentiation. Endocrinology 144, 2559-2565. https://doi.org/10.1210/en.2002-220894