Abstract：Sterol regulatory element binding proteins (SREBPs) are the major transcription factors regulating cholesterol, fatty acid and triglyceride biosynthesis and control the expression of key genes such as lipogenesis and uptake. In this review, we summarize the processing of SREBPs and their interactions with insulin, cyclic adenosine monophosphate (cAMP), and liver X receptor (LXR) for the synthesis and metabolism of lipid, and combine the latest researches to illustrate the function of SREBPs. These findings suggest that inhibition of SREBPs can be a new strategy for the treatment of metabolic diseases, such as type Ⅱ diabetes, insulin resistance, fatty liver, atherosclerosis and tumors.
TAGHIBIGLOU C, MARTIN H G S, LAI T W, et al. Role of NMDA receptor-dependent activation of SREBP1 in excitotoxic and ischemic neuronal injuries [J] . Nat Med, 2009, 15(12):1399-1406.
[2]
TAGHIBIGLOU C, MARTIN H G, ROSE J K, et al. Essential role of SBP-1 activation in oxygen deprivation induced lipid accumulation and increase in body width/length ratio in Caenorhabditis elegans [J] . FEBS Lett, 2009, 583(4):831-834.
[3]
KAMISUKI S, MAO Q, ABU-ELHEIGA L, et al. A small molecule that blocks fat synthesis by inhibiting the activation of SREBP [J] . Chem Biol, 2009, 16(8):882-892.
[4]
ROHRIG F, SCHULZE A. The multifaceted roles of fatty acid synthesis in cancer [J] . Nat Rev Cancer, 2016, 16(11):732-749.
[5]
SODI V L, BACIGALUPA Z A, FERRER C M, et al. Nutrient sensor O-GlcNAc transferase controls cancer lipid metabolism via SREBP-1 regulation [J] . Oncogene, 2018, 37(7):924-934.
[6]
SWINNEN J V, HEEMERS1 H, DEBOEL L, et al. Stimulation of tumor-associated fatty acid synthase expression by growth factor activation of the sterol regulatory element-binding protein pathway [J] . Oncogene, 2000, 19(25):5173-5181.
[7]
CHAE H S, YOU B H, KIM D Y, et al. Sauchinone controls hepatic cholesterol homeostasis by the negative regulation of PCSK9 transcriptional network [J] . Sci Rep, 2018, 8(1):6737-6751.
[8]
LI YING Z L. Anti-obesity effects of alcohol extract from Abelmoschus esculentus Linn. and its correlation with gene SREBP-1 and FAS[J] . Chin Pharm J(中国药学杂志), 2017, 52(23):2087-2091.
[9]
YANG M Y, CHAN K C, LEE Y J, et al. Sechium edule shoot extracts and active components improve obesity and a fatty liver that involved reducing hepatic lipogenesis and adipogenesis in high-fat-diet-fed rats [J] . J Agric Food Chem, 2015, 63(18):4587-4596.
[10]
XIAO X, SONG B L. SREBP: a novel therapeutic target [J] . Acta Biochim Et Biophys Sin, 2012, 45(1):2-10.
[11]
KAMISUKI S, SHIRAKAWA T, KUGIMIYA A, et al. Synthesis and evaluation of diarylthiazole derivatives that Inhibit activation of sterol regulatory element-binding proteins[J] . J Med Chem, 2011, 54(13):4923-4927.
[12]
SATO R. Sterol metabolism and SREBP activation [J] . Arch Biochem Biophys, 2010, 501(2):177-181.
[13]
LEE J Z, ZHOU J, XIE W. PXR and LXR in hepatic steatosis: a new dog and an old dog with new tricks [J] . Mol Pharm, 2008, 5(1):60-66.
[14]
RAWSON R B. The SREBP pathway--insights from insigs and insects [J] . Nat Rev Mol Cell Biol, 2003, 4(8):631-640.
[15]
LIN JINMEI D L, SONG BAOLIANG. Effects of chrysophanol on expression of SREBPS and lipid metabolism in Huh-7 cells [J] . Acta Pharm Sin(药学学报), 2015, 50(2):174-179.
[16]
LAI C S, HO M H, TSAI M L. Suppression of adipogenesis and obesity in high-fat induced mouse model by hydroxylated polymethoxyflavones[J] . J Agric Food Chem, 2013, 61(43):10320-10328.
[17]
LEHR S, KOTZKA J, AVCI H, et al. Effect of sterol regulatory element binding protein-1a on the mitochondrial protein pattern in human liver cells detected by 2D-DIGE [J] . Biochem, 2005, 44(13):5117-5128.
[18]
XU D, WANG Z, ZHANG Y, et al. PAQR3 modulates cholesterol homeostasis by anchoring Scap/SREBP complex to the golgi apparatus [J] . Nat Commun, 2015, 6(1):8100-8115.
[19]
LEE J H, KANG H S, PARK H Y, et al. PPARalpha-dependent Insig2a overexpression inhibits SREBP-1c processing during fasting [J] . Sci Rep, 2017, 7(1):9958-9970.
[20]
IDE T, SHIMANO H, YAHAGI N, et al. SREBPs suppress IRS-2-mediated insulin signalling in the liver [J] . Nat Cell Biol, 2004, 6(4):351-357.
[21]
HASHIMOTO T I, TAKASHI. Activity and mRNA levels of enzymes involved in hepatic fatty acid synthesis in rats fed naringenin [J] . J Agric Food Chem, 2015, 63(43):9536-9542.
[22]
YAN C, CHEN J, CHEN N. Long noncoding RNA MALAT1 promotes hepatic steatosis and insulin resistance by increasing nuclear SREBP-1c protein stability [J] . Sci Rep, 2016, 6(3):22640-22651.
[23]
RICOULT S J, YECIES J L, BEN-SAHRA I, et al. Oncogenic PI3K and K-Ras stimulate de novo lipid synthesis through mTORC1 and SREBP [J] . Oncogene, 2016, 35(10):1250-1260.
[24]
KELSEY I, ZBINDEN M, BYLES V, et al. mTORC1 suppresses PIM3 expression via miR-33 encoded by the SREBP loci [J] . Sci Rep, 2017, 7(1):16112-16123.
[25]
YELLATURU C R, DENG X, CAGEN L M, et al. Insulin enhances post-translational processing of nascent SREBP-1c by promoting its phosphorylation and association with COPⅡ vesicles [J] . J Biol Chem, 2009, 284(12):7518-7532.
[26]
PUNGA T, BENGOECHEA-ALONSO M T, ERICSSON J. Phosphorylation and ubiquitination of the transcription factor sterol regulatory element-binding protein-1 in response to DNA binding [J] . J Biol Chem, 2006, 281(35):25278-25286.
[27]
SUNDQVIST A, BENGOECHEA-ALONSO M T, YE X, et al. Control of lipid metabolism by phosphorylation-dependent degradation of the SREBP family of transcription factors by SCF(Fbw7) [J] . Cell Metab, 2005, 1(6):379-391.
[28]
LIU X M, WANG B C, DENG C. The second-generation antipsychotic drugs induced dyslipidemia: a review of research and mechanisms [J] . Chin Pharm J(中国药学杂志), 2016, 51(3):172-176.
[29]
HORIE T, NISHINO T, BABA O, et al. MicroRNA-33 regulates sterol regulatory element-binding protein 1 expression in mice [J] . Nat Commun, 2013, 4:2883.
[30]
LIU L, ZHAO X P, ZHAO L, et al. Arginine methylation of SREBP1a via PRMT5 promotes de novo lipogenesis and tumor growth [J] . Cancer Res, 2016, 76(5):1260-1272.
[31]
ZHU Z, ZHAO X, ZHAO L, et al. p54/NONO regulates lipid metabolism and breast cancer growth through SREBP-1A [J] . Oncogene, 2015, 35:1399-1410.
[32]
PETERSON T R, SENGUPTA S S, HARRIS T E, et al. mTOR Complex 1 regulates lipin 1 localization to control the SREBP pathway [J] . Cell, 2011, 146(3):408-420.
[33]
JIN Q, YUAN L X, BOULBES D, et al. Fatty acid synthase phosphorylation: a novel therapeutic target in HER2-overexpressing breast cancer cells [J] . Breast Cancer Res, 2010, 12(6):R96.
[34]
TANG J J, LI J G, QI W, et al. Inhibition of SREBP by a small molecule, betulin, improves hyperlipidemia and insulin resistance and reduces atherosclerotic plaques [J] . Cell Metab, 2011, 13(1):44-56.
[35]
CHEN M, ZHANG J, SAMPIERI K, et al. An aberrant SREBP-dependent lipogenic program promotes metastatic prostate cancer [J] . Nat Genet, 2018, 50(2):206-218.
[36]
ZHU Z, ZHAO X, ZHAO L, et al. p54(nrb)/NONO regulates lipid metabolism and breast cancer growth through SREBP-1A [J] . Oncogene, 2016, 35(11):1399-1410.
[37]
MOON Y A, LIANG G, XIE X, et al. The Scap/SREBP pathway is essential for developing diabetic fatty liver and carbohydrate-induced hypertriglyceridemia in animals [J] . Cell Metab, 2012, 15(2):240-246.
[38]
LIU T F, TANG J J, LI B L, et al. Ablation of gp78 in liver improves hyperlipidemia and insulin resistance by inhibiting SREBP to decrease lipid biosynthesis[J] . Cell Metab, 2012, 16(2):213-225.
2019, Vol. 54 
