Sánchez-Solana Beatriz, Li Da-Qiang, Kumar Rakesh
Department of Biochemistry and Molecular Medicine, School of Medicine and Health Sciences, The George Washington University, Washington, DC 20037, USA.
Department of Biochemistry and Molecular Medicine, School of Medicine and Health Sciences, The George Washington University, Washington, DC 20037, USA.
Biochim Biophys Acta. 2014 Feb;1843(2):316-26. doi: 10.1016/j.bbamcr.2013.11.012. Epub 2013 Nov 25.
Microrchidia (MORC) family CW-type zinc finger 2 (MORC2) has been shown to be involved in several nuclear processes, including transcription modulation and DNA damage repair. However, its cytosolic function remains largely unknown. Here, we report an interaction between MORC2 and adenosine triphosphate (ATP)-citrate lyase (ACLY), an enzyme that catalyzes the formation of acetyl-coA and plays a central role in lipogenesis, cholesterogenesis, and histone acetylation. Furthermore, we demonstrate that MORC2 promotes ACLY activation in the cytosol of lipogenic breast cancer cells and plays an essential role in lipogenesis, adipogenesis and differentiation of 3T3-L1 preadipocytic cells. Consistently, the expression of MORC2 is induced during the process of 3T3-L1 adipogenic differentiation and mouse mammary gland development at a stage of increased lipogenesis. This observation was accompanied by a high ACLY activity. Together, these results demonstrate a cytosolic function of MORC2 in lipogenesis, adipogenic differentiation, and lipid homeostasis by regulating the activity of ACLY.
微小染色体相关蛋白(MORC)家族CW型锌指蛋白2(MORC2)已被证明参与多种核过程,包括转录调控和DNA损伤修复。然而,其胞质功能在很大程度上仍不清楚。在此,我们报告了MORC2与三磷酸腺苷(ATP)-柠檬酸裂解酶(ACLY)之间的相互作用,ACLY是一种催化乙酰辅酶A形成的酶,在脂肪生成、胆固醇生成和组蛋白乙酰化中起核心作用。此外,我们证明MORC2促进脂肪生成的乳腺癌细胞胞质中ACLY的激活,并在3T3-L1前脂肪细胞的脂肪生成、脂肪形成和分化中起重要作用。一致的是,在3T3-L1脂肪生成分化过程以及小鼠乳腺发育脂肪生成增加阶段,MORC2的表达被诱导。这一观察结果伴随着较高的ACLY活性。总之,这些结果证明了MORC2通过调节ACLY的活性在脂肪生成、脂肪形成分化和脂质稳态中发挥胞质功能。