title: S-nitrosylation of fatty acid synthase regulates its activity through dimerization.
abstract: NO regulates a variety of physiological processes, including cell proliferation, differentiation, and inflammation. S-nitrosylation, a NO-mediated reversible protein modification, leads to changes in the activity and function of proteins. In particular, the role of S-nitrosylation during adipogenesis is largely unknown. We hypothesized that the normal physiological levels of NO, but not the excess levels generated under severe conditions, such as inflammation, may be critically involved in the proper regulation of adipogenesis. We found that endogenous S-nitrosylation of proteins was required for adipocyte differentiation. By performing a biotin-switch assay, we identified FAS, a key lipogenic enzyme in adipocytes, as a target of S-nitrosylation during adipogenesis. Interestingly, we also observed that the dimerization of FAS increased in parallel with the amount of S-nitrosylated FAS during adipogenesis. In addition, we found that exogenous NO enhanced the dimerization and the enzymatic activity of FAS. Moreover, site-directed mutagenesis of three predicted S-nitrosylation sites indicated that S-nitrosylation of FAS at Cys(1471)and Cys(2091), but not at Cys(1127), increased its enzymatic activity. Taken together, these results suggest that the S-nitrosylation of FAS at normal physiological levels of NO increases its activity through dimerization and may contribute to the proper regulation of adipogenesis.
authors: Basic Research and Innovation Division, Amorepacific Corporation R&D Center, 314-1, Bora-dong, Giheung-gu, Yongin-si, Gyeonggi-do 446-729, Republic of Korea.
authors: Min Sik
authors: MS
authors: Choi
authors: Basic Research and Innovation Division, Amorepacific Corporation R&D Center, 314-1, Bora-dong, Giheung-gu, Yongin-si, Gyeonggi-do 446-729, Republic of Korea.
authors: Ji-Yong
authors: JY
authors: Jung
authors: Basic Research and Innovation Division, Amorepacific Corporation R&D Center, 314-1, Bora-dong, Giheung-gu, Yongin-si, Gyeonggi-do 446-729, Republic of Korea.
authors: Hyoung-June
authors: HJ
authors: Kim
authors: Basic Research and Innovation Division, Amorepacific Corporation R&D Center, 314-1, Bora-dong, Giheung-gu, Yongin-si, Gyeonggi-do 446-729, Republic of Korea.
authors: Mi Ra
authors: MR
authors: Ham
authors: Basic Research and Innovation Division, Amorepacific Corporation R&D Center, 314-1, Bora-dong, Giheung-gu, Yongin-si, Gyeonggi-do 446-729, Republic of Korea biopang@empal.com TRLee@amorepacific.com.
authors: Tae Ryong
authors: TR
authors: Lee
authors: Basic Research and Innovation Division, Amorepacific Corporation R&D Center, 314-1, Bora-dong, Giheung-gu, Yongin-si, Gyeonggi-do 446-729, Republic of Korea biopang@empal.com TRLee@amorepacific.com.
authors: Dong Wook
authors: DW
authors: Shin
mesh_terms: D017667:Adipocytes / Q000166:cytology; D050156:Adipogenesis; D003545:Cysteine / Q000378:metabolism; D004789:Enzyme Activation; D064429:Fatty Acid Synthases / Q000737:chemistry* / Q000378:metabolism*; D057809:HEK293 Cells; D006801:Humans; D009569:Nitric Oxide / Q000378:metabolism*; D055503:Protein Multimerization; D011499:Protein Processing, Post-Translational; D020836:Protein Structure, Quaternary; D013455:Sulfur / Q000378:metabolism
chemical_list: D009569:Nitric Oxide; D013455:Sulfur; D064429:Fatty Acid Synthases; D003545:Cysteine
keywords: adipocyte; adipogenesis; nitric oxide