Hansenula polymorpha Hac1p Is Critical to Protein N-Glycosylation Activity Modulation, as Revealed by Functional and Transcriptomic Analysesopen access
- Authors
- Moon, Hye-Yun; Cheon, Seon Ah; Kim, Hyunah; Agaphonov, M.O.; Kwon, Ohsuk; Oh, Doo-Byoung; Kim, Jeong-Yoon; Kang, Hyun Ah
- Issue Date
- Oct-2015
- Publisher
- AMER SOC MICROBIOLOGY
- Citation
- APPLIED AND ENVIRONMENTAL MICROBIOLOGY, v.81, no.20, pp 6982 - 6993
- Pages
- 12
- Journal Title
- APPLIED AND ENVIRONMENTAL MICROBIOLOGY
- Volume
- 81
- Number
- 20
- Start Page
- 6982
- End Page
- 6993
- URI
- https://scholarworks.bwise.kr/cau/handle/2019.sw.cau/9053
- DOI
- 10.1128/AEM.01440-15
- ISSN
- 0099-2240
1098-5336
- Abstract
- 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 (Hphac1 Delta) 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 Hphac1 Delta 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 Hphac1 Delta 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.
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