Lysine fatty acylation promotes lysosomal targeting of TNF-α

Hong Jiang; Xiaoyu Zhang; Hening Lin

doi:10.1038/srep24371

Lysine fatty acylation promotes lysosomal targeting of TNF-α

Hong Jiang, Xiaoyu Zhang, Hening Lin^*

^*Corresponding author for this work

Chemistry

Research output: Contribution to journal › Article › peer-review

33 Scopus citations

Abstract

Tumor necrosis factor-α (TNF-α) is a proinflammation cytokine secreted by various cells. Understanding its secretive pathway is important to understand the biological functions of TNF-α and diseases associated with TNF-α. TNF-α is one of the first proteins known be modified by lysine fatty acylation (e.g. myristoylation). We previously demonstrated that SIRT6, a member of the mammalian sirtuin family of enzymes, can remove the fatty acyl modification on TNF-α and promote its secretion. However, the mechanistic details about how lysine fatty acylation regulates TNF-α secretion have been unknown. Here we present experimental data supporting that lysine fatty acylation promotes lysosomal targeting of TNF-α. The result is an important first step toward understanding the biological functions of lysine fatty acylation.

Original language	English (US)
Article number	24371
Journal	Scientific reports
Volume	6
DOIs	https://doi.org/10.1038/srep24371
State	Published - Apr 15 2016

Funding

We thank Professor Barbara A. Baird for providing the pEGFP-N1 vector, Dr. Frederick Maxfield and Dr. Fenghua Hu for helpful discussions. Imaging data was acquired in the Cornell BRC-Imaging Facility using the shared, NYSTEM (CO29155) and NIH (S10OD018516)-funded Zeiss LSM880 confocal/multiphoton microscope. This work was supported in part by grants from NIH to H.L. (GM086703 and DK107868).

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title = "Lysine fatty acylation promotes lysosomal targeting of TNF-α",

abstract = "Tumor necrosis factor-α (TNF-α) is a proinflammation cytokine secreted by various cells. Understanding its secretive pathway is important to understand the biological functions of TNF-α and diseases associated with TNF-α. TNF-α is one of the first proteins known be modified by lysine fatty acylation (e.g. myristoylation). We previously demonstrated that SIRT6, a member of the mammalian sirtuin family of enzymes, can remove the fatty acyl modification on TNF-α and promote its secretion. However, the mechanistic details about how lysine fatty acylation regulates TNF-α secretion have been unknown. Here we present experimental data supporting that lysine fatty acylation promotes lysosomal targeting of TNF-α. The result is an important first step toward understanding the biological functions of lysine fatty acylation.",

author = "Hong Jiang and Xiaoyu Zhang and Hening Lin",

note = "Funding Information: We thank Professor Barbara A. Baird for providing the pEGFP-N1 vector, Dr. Frederick Maxfield and Dr. Fenghua Hu for helpful discussions. Imaging data was acquired in the Cornell BRC-Imaging Facility using the shared, NYSTEM (CO29155) and NIH (S10OD018516)-funded Zeiss LSM880 confocal/multiphoton microscope. This work was supported in part by grants from NIH to H.L. (GM086703 and DK107868).",

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AU - Zhang, Xiaoyu

AU - Lin, Hening

N1 - Funding Information: We thank Professor Barbara A. Baird for providing the pEGFP-N1 vector, Dr. Frederick Maxfield and Dr. Fenghua Hu for helpful discussions. Imaging data was acquired in the Cornell BRC-Imaging Facility using the shared, NYSTEM (CO29155) and NIH (S10OD018516)-funded Zeiss LSM880 confocal/multiphoton microscope. This work was supported in part by grants from NIH to H.L. (GM086703 and DK107868).

PY - 2016/4/15

Y1 - 2016/4/15

N2 - Tumor necrosis factor-α (TNF-α) is a proinflammation cytokine secreted by various cells. Understanding its secretive pathway is important to understand the biological functions of TNF-α and diseases associated with TNF-α. TNF-α is one of the first proteins known be modified by lysine fatty acylation (e.g. myristoylation). We previously demonstrated that SIRT6, a member of the mammalian sirtuin family of enzymes, can remove the fatty acyl modification on TNF-α and promote its secretion. However, the mechanistic details about how lysine fatty acylation regulates TNF-α secretion have been unknown. Here we present experimental data supporting that lysine fatty acylation promotes lysosomal targeting of TNF-α. The result is an important first step toward understanding the biological functions of lysine fatty acylation.

AB - Tumor necrosis factor-α (TNF-α) is a proinflammation cytokine secreted by various cells. Understanding its secretive pathway is important to understand the biological functions of TNF-α and diseases associated with TNF-α. TNF-α is one of the first proteins known be modified by lysine fatty acylation (e.g. myristoylation). We previously demonstrated that SIRT6, a member of the mammalian sirtuin family of enzymes, can remove the fatty acyl modification on TNF-α and promote its secretion. However, the mechanistic details about how lysine fatty acylation regulates TNF-α secretion have been unknown. Here we present experimental data supporting that lysine fatty acylation promotes lysosomal targeting of TNF-α. The result is an important first step toward understanding the biological functions of lysine fatty acylation.

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Lysine fatty acylation promotes lysosomal targeting of TNF-α

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