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Correction published on 10 February 2021, see Int. J. Mol. Sci. 2021, 22(4), 1751.
Article

Tip60 Phosphorylation at Ser 99 Is Essential for Autophagy Induction in Bombyx mori

1
Guangdong Provincial Key Laboratory of Agro-Animal Genomics and Molecular Breeding/Guangdong Provincial Sericulture and Mulberry Engineering Research Center, College of Animal Science, South China Agricultural University, Guangzhou 510642, China
2
Guangdong Province Key Laboratory for Biotechnology Drug Candidates, School of Life Sciences and Biopharmaceutics, Guangdong Pharmaceutical University, Guangzhou 510006, China
3
Guangdong Provincial Key Laboratory of Insect Developmental Biology and Applied Technology, Institute of Insect Science and Technology, School of Life Sciences, South China Normal University, Guangzhou 510631, China
4
The Sericultural and Agri-Food Research Institute of the Guangdong Academy of Agricultural Sciences, Guangzhou 510610, China
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2020, 21(18), 6893; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21186893
Received: 26 July 2020 / Revised: 17 September 2020 / Accepted: 18 September 2020 / Published: 20 September 2020
(This article belongs to the Special Issue Molecular Ecology, Physiology and Biochemistry of Insects 2.0)
Tip60, a key histone acetyltransferase of the MYST family and member of the nuclear multimeric protein complex (NuA4), regulates the activity and stability of proteins involved in the cell cycle, DNA damage responses, autophagy, etc. However, the function and regulatory mechanism of Tip60 homolog in Bombyx mori are not elucidated. In the present study, Bombyx Tip60 (BmTip60) was functionally identified. Developmental profiles showed that the protein levels and nuclear localization of BmTip60 peaked in fat body during the larval–pupal metamorphosis when autophagy was intensive; simultaneously, the BmTip60 protein migrated to form an upper band as detected by Western blot. Interestingly, the upper band of BmTip60 was reduced by λ-phosphatase treatment, indicating that it was a phosphorylated form of BmTip60. Results showed that BmTip60 was promoted by starvation but not 20-hydroxyecdysone treatment. Transcription factor AMP-activated protein kinase (AMPK) affected by starvation was pivotal for BmTip60 protein migration. In addition, one mammalian phosphorylation site was identified in BmTip60 at Ser99, the constitutive-activation mutation of Ser99 to Asp99 but not its inactive mutation to Ala99 significantly upregulated autophagy, showing the critical role of phosphorylation at Ser99 for BmTip60-mediated autophagy. In conclusion, the starvation-AMPK axis promotes BmTip60 in B. mori, which was requisite for autophagy induction. These results reveal a regulatory mechanism of histone acetyltransferase Tip60 homologs by phosphorylation in insects, and sheds light on further related studies of acetylation regulation. View Full-Text
Keywords: BmTip60; autophagy; Bombyx mori; AMP-activated protein kinase; starvation BmTip60; autophagy; Bombyx mori; AMP-activated protein kinase; starvation
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MDPI and ACS Style

Wu, W.; Li, K.; Zhao, H.; Xu, X.; Xu, J.; Luo, M.; Xiao, Y.; Tian, L. Tip60 Phosphorylation at Ser 99 Is Essential for Autophagy Induction in Bombyx mori. Int. J. Mol. Sci. 2020, 21, 6893. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21186893

AMA Style

Wu W, Li K, Zhao H, Xu X, Xu J, Luo M, Xiao Y, Tian L. Tip60 Phosphorylation at Ser 99 Is Essential for Autophagy Induction in Bombyx mori. International Journal of Molecular Sciences. 2020; 21(18):6893. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21186893

Chicago/Turabian Style

Wu, Wenmei, Kang Li, Haigang Zhao, Xianying Xu, Jing Xu, Man Luo, Yang Xiao, and Ling Tian. 2020. "Tip60 Phosphorylation at Ser 99 Is Essential for Autophagy Induction in Bombyx mori" International Journal of Molecular Sciences 21, no. 18: 6893. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21186893

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