Hansenula polymorpha Hac1p is critical to protein N-glycosylation activity modulation, as revealed by functional and transcriptomic analyses
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- Hansenula polymorpha Hac1p is critical to protein N-glycosylation activity modulation, as revealed by functional and transcriptomic analyses
- H Y Moon; S A Cheon; H Kim; M O Agaphonov; Oh Suk Kwon; Doo-Byoung Oh; J Y Kim; H A Kang
- Bibliographic Citation
- Applied and Environmental Microbiology, vol. 81, no. 20, pp. 6982-6993
- Publication Year
- Aggregation of misfolded protein in the endoplasmic reticulum (ER) induces a cellular protective response to ER stress, the unfolded protein response (UPR), which is mediated by a basic leucine zipper (bZIP) transcription factor, Hac1p/Xbp1. In this study, we identified and studied the molecular functions of a HAC1 homolog from the thermotolerant yeast Hansenula polymorpha (HpHAC1). We found that the HpHAC1 mRNA contains a nonconventional intron of 177 bp whose interaction with the 5' untranslated region is responsible for the translational inhibition of the HpHAC1 mRNA. The H. polymorpha hac1-null (Hphac1Δ) mutant strain grew slowly, even under normal growth conditions, and was less thermotolerant than the wild-type (WT) strain. The mutant strain was also more sensitive to cell wall-perturbing agents and to the UPR-inducing agents dithiothreitol (DTT) and tunicamycin (TM). Using comparative transcriptome analysis of the WT and Hphac1Δ strains treated with DTT and TM, we identified HpHAC1-dependent core UPR targets, which included genes involved in protein secretion and processing, particularly those required for N-linked protein glycosylation. Notably, different glycosylation and processing patterns of the vacuolar glycoprotein carboxypeptidase Y were observed in the WT and Hphac1Δ strains. Moreover, overexpression of active HpHac1p significantly increased the N-linked glycosylation efficiency and TM resistance. Collectively, our results suggest that the function of HpHac1p is important not only for UPR induction but also for efficient glycosylation in H. polymorpha.
- Amer Soc Microb
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- Division of Bio Technology Innovation > SME Support Center > 1. Journal Articles
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