title: ATF4 regulates SREBP1c expression to control fatty acids synthesis in 3T3-L1 adipocytes differentiation.
abstract: Activating transcription factor 4 (ATF4), which is highly expressed in 3T3-L1 adipocytes after adipogenic induction, is essential for adipocytes differentiation. ATF4 also plays a vital role in regulating fatty acids biosynthesis, whereas the detailed mechanism of this process is still unclear. Here we demonstrated that siRNA-based ATF4 depletion in 3T3-L1 adipocytes significantly reduced the accumulation of fatty acids and triglycerides. Moreover, SREBP1c protein, which is an important transcription factor of lipogenesis, appreciably decreased while Srebp1c mRNA increased. Then we identified that ATF4 could maintain SREBP1c protein stability by directly activating the expression of USP7 which deubiquitinates SREBP1c and increases its protein content in cell. Besides, USP7 could restore the synthesis of fatty acids and triglycerides in the absence of ATF4. On the other hand, we found that ATF4 might inhibit the transcription of Srebp1c through TRB3, which is repressed by IBMX and DEX during early adipogenesis. Thus, our data indicate that ATF4 regulates SREBP1c expression to control fatty acids synthesis.
authors.affiliation: State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou, China.
authors.forename: Hu
authors.initials: H
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou, China.
authors.forename: Renqiang
authors.initials: R
authors.lastname: Yuan
authors.affiliation: State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou, China.
authors.forename: Xumeng
authors.initials: X
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou, China.
authors.forename: Luxi
authors.initials: L
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou, China.
authors.forename: Xingyu
authors.initials: X
authors.lastname: Zhou
authors.affiliation: State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou, China.
authors.forename: Zhuning
authors.initials: Z
authors.lastname: Yuan
authors.affiliation: State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou, China.
authors.forename: Yaping
authors.initials: Y
authors.lastname: Nie
authors.affiliation: State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Li
authors.affiliation: State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou, China. Electronic address: modelin@mail.sysu.edu.cn.
authors.forename: Delin
authors.initials: D
authors.lastname: Mo
authors.affiliation: State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou, China. Electronic address: chyaosh@mail.sysu.edu.cn.
authors.forename: Yaosheng
authors.initials: Y
authors.lastname: Chen
mesh_terms: D041721:3T3-L1 Cells; D051701:Activating Transcription Factor 4 / Q000502:physiology*; D017667:Adipocytes / Q000166:cytology*; D000818:Animals; D002454:Cell Differentiation; D005227:Fatty Acids / Q000096:biosynthesis*; D051379:Mice; D051780:Sterol Regulatory Element Binding Protein 1 / Q000378:metabolism*; D014158:Transcription, Genetic / Q000502:physiology; D000076084:Ubiquitin-Specific Peptidase 7; D064570:Ubiquitin-Specific Proteases / Q000378:metabolism
chemical_list: C081452:Atf4 protein, mouse; D005227:Fatty Acids; C497388:Srebf1 protein, mouse; D051780:Sterol Regulatory Element Binding Protein 1; D051701:Activating Transcription Factor 4; D000076084:Ubiquitin-Specific Peptidase 7; D064570:Ubiquitin-Specific Proteases; C579190:Usp7 protein, mouse
keywords: ATF4; PTM; SREBP1c; TRB3; Transcription; USP7