title: Monocyte chemotactic protein-induced protein 1 (MCPIP1) suppresses stress granule formation and determines apoptosis under stress.
abstract: It is unclear how stress granule (SG) formation and cellular apoptosis are coordinately regulated. MCPIP1 (monocyte chemotactic protein-induced protein 1), also known as Zc3h12a, is a critical regulator of the inflammatory response and immune homeostasis. However, the role of MCPIP1 in stress response remains unknown. Here, we report that overexpression of MCPIP1 inhibited the assembly of SGs in response to various stresses. Conversely, MCPIP1-deficient splenocytes developed more SGs even without stress. On the other hand, overexpression of MCPIP1 sensitized RAW 264.7 cells to apoptosis under stress, whereas MCPIP1-deficient cells were resistant to stress-induced apoptosis. Mutagenesis study showed that the ability of MCPIP1 to repress SG formation is dependent on its deubiquitinating activity. Consistently, MCPIP1 negatively regulated stress-induced phosphorylation of eIF2α and thus released stress-induced inhibition of protein translation. However, MCPIP1 also inhibited 15-deoxy-Δ(12,14)-prostaglandin J(2)-induced SG formation, which was reported to be independent of eIF2α phosphorylation. Taken together, these results suggest that MCPIP1 coordinates SG formation and apoptosis during cellular stress and may play a critical role in immune homeostasis and resolution of macrophage inflammation.
authors.affiliation: Shock/Trauma Research Center and Department of Basic Medical Science, School of Medicine, University of Missouri-Kansas City, Kansas City, Missouri 64108.
authors.forename: Dongfei
authors.initials: D
authors.lastname: Qi
authors.affiliation: Shock/Trauma Research Center and Department of Basic Medical Science, School of Medicine, University of Missouri-Kansas City, Kansas City, Missouri 64108.
authors.forename: Shengping
authors.initials: S
authors.lastname: Huang
authors.affiliation: Shock/Trauma Research Center and Department of Basic Medical Science, School of Medicine, University of Missouri-Kansas City, Kansas City, Missouri 64108.
authors.forename: Ruidong
authors.initials: R
authors.lastname: Miao
authors.affiliation: Cancer Center, Sanford-Burnham Medical Research Institute, La Jolla, California 92037.
authors.forename: Zhi-Gang
authors.initials: ZG
authors.lastname: She
authors.affiliation: Shock/Trauma Research Center and Department of Basic Medical Science, School of Medicine, University of Missouri-Kansas City, Kansas City, Missouri 64108.
authors.forename: Tim
authors.initials: T
authors.lastname: Quinn
authors.affiliation: Department of Pharmacology, A. T. Still University of Health Sciences, Kirksville, Missouri 63501.
authors.forename: Yingzi
authors.initials: Y
authors.lastname: Chang
authors.affiliation: Department of Internal Medicine, Saint Louis University School of Medicine, St. Louis, Missouri 63104.
authors.forename: Jianguo
authors.initials: J
authors.lastname: Liu
authors.affiliation: Department of Cell Biology and Anatomy, University of South Carolina, Columbia, South Carolina 29209.
authors.forename: Daping
authors.initials: D
authors.lastname: Fan
authors.affiliation: Cardiovascular Center, Department of Internal Medicine, University of Michigan Medical Center, Ann Arbor, Michigan 48109.
authors.forename: Y Eugene
authors.initials: YE
authors.lastname: Chen
authors.affiliation: Shock/Trauma Research Center and Department of Basic Medical Science, School of Medicine, University of Missouri-Kansas City, Kansas City, Missouri 64108. Electronic address: fum@umkc.edu.
authors.forename: Mingui
authors.initials: M
authors.lastname: Fu
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D057809:HEK293 Cells; D006367:HeLa Cells; D006706:Homeostasis / Q000502:physiology*; D006801:Humans; D008264:Macrophages / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D016296:Mutagenesis; D012260:Ribonucleases / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D013312:Stress, Physiological / Q000502:physiology*; D014157:Transcription Factors / Q000235:genetics / Q000276:immunology / Q000378:metabolism*
chemical_list: D014157:Transcription Factors; D012260:Ribonucleases; C510646:ZC3H12A protein, human; C541320:Zc3h12a protein, mouse