Aggregation of Human S100A8 and S100A9 Amyloidogenic Proteins Perturbs Proteostasis in a Yeast Model

被引:18
|
作者
Eremenko, Ekaterina [1 ]
Ben-Zvi, Anat [1 ,2 ]
Morozova-Roche, Ludmilla A. [3 ]
Raveh, Dina [1 ]
机构
[1] Ben Gurion Univ Negev, Dept Life Sci, IL-84105 Beer Sheva, Israel
[2] Ben Gurion Univ Negev, Natl Inst Biotechnol Negev, IL-84105 Beer Sheva, Israel
[3] Umea Univ, Dept Med Biochem & Biophys, S-90187 Umea, Sweden
来源
PLOS ONE | 2013年 / 8卷 / 03期
关键词
UBIQUITIN-PROTEASOME SYSTEM; URE3 PRION PROPAGATION; EF-HAND PROTEINS; SACCHAROMYCES-CEREVISIAE; QUALITY-CONTROL; NEURODEGENERATIVE DISEASE; MOLECULAR CHAPERONES; HUNTINGTIN TOXICITY; MUTANT HUNTINGTIN; GENE-EXPRESSION;
D O I
10.1371/journal.pone.0058218
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Amyloid aggregates of the calcium-binding EF-hand proteins, S100A8 and S100A9, have been found in the corpora amylacea of patients with prostate cancer and may play a role in carcinogenesis. Here we present a novel model system using the yeast Saccharomyces cerevisiae to study human S100A8 and S100A9 aggregation and toxicity. We found that S100A8, S100A9 and S100A8/9 cotransfomants form SDS-resistant non-toxic aggregates in yeast cells. Using fluorescently tagged proteins, we showed that S100A8 and S100A9 accumulate in foci. After prolonged induction, S100A8 foci localized to the cell vacuole, whereas the S100A9 foci remained in the cytoplasm when present alone, but entered the vacuole in cotransformants. Biochemical analysis of the proteins indicated that S100A8 and S100A9 alone or coexpressed together form amyloid-like aggregates in yeast. Expression of S100A8 and S100A9 in wild type yeast did not affect cell viability, but these proteins were toxic when expressed on a background of unrelated metastable temperature-sensitive mutant proteins, Cdc53-1p, Cdc34-2p, Srp1-31p and Sec27-1p. This finding suggests that the expression and aggregation of S100A8 and S100A9 may limit the capacity of the cellular proteostasis machinery. To test this hypothesis, we screened a set of chaperone deletion mutants and found that reducing the levels of the heat-shock proteins Hsp104p and Hsp70p was sufficient to induce S100A8 and S100A9 toxicity. This result indicates that the chaperone activity of the Hsp104/Hsp70 bi-chaperone system in wild type cells is sufficient to reduce S100A8 and S100A9 amyloid toxicity and preserve cellular proteostasis. Expression of human S100A8 and S100A9 in yeast thus provides a novel model system for the study of the interaction of amyloid deposits with the proteostasis machinery.
引用
收藏
页数:14
相关论文
共 50 条
  • [21] Regulation of myeloid cell differentiation by S100A8 and S100A9
    Defrene, J.
    Laouedj, M.
    Cesaro, A.
    Page, N.
    Barabe, F.
    Tessier, P.
    EUROPEAN JOURNAL OF IMMUNOLOGY, 2016, 46 : 322 - 322
  • [22] Control of endogenous stress proteins S100A8 and S100A9 in innate and adaptive immunity
    Vogl, T.
    EUROPEAN JOURNAL OF CLINICAL INVESTIGATION, 2013, 43 : 4 - 5
  • [23] Crosslinking of microtubules and actin filaments by S100A8/S100A9
    M Wolf
    C Riethmüller
    B Petersen
    H Oberleithner
    J Roth
    T Vogl
    Cell Communication and Signaling, 7 (Suppl 1)
  • [24] The role of S100A8, S100A9 and Calprotectin in skin inflammation
    Irigoyen, M. Palomo
    Bakiri, L.
    Wagner, E. F.
    FEBS OPEN BIO, 2022, 12 : 39 - 39
  • [25] S100A8 and S100A9: New Insights into Their Roles in Malignancy
    Srikrishna, Geetha
    JOURNAL OF INNATE IMMUNITY, 2012, 4 (01) : 31 - 40
  • [26] The role of S100A8, S100A9 and Calprotectin in skin inflammation
    Irigoyen, M. P.
    Bakiri, L.
    EXPERIMENTAL DERMATOLOGY, 2021, 30 : 6 - 7
  • [27] SenoIndex: S100A8/S100A9 as a novel aging biomarker
    Zhang, Baohu
    Yan, Haoteng
    Liu, Xiaoqian
    Sun, Liang
    Ma, Shuai
    Wang, Si
    Qu, Jing
    Liu, Guang-Hui
    Zhang, Weiqi
    LIFE MEDICINE, 2023, 2 (04):
  • [28] S100A8 and S100A9 positive cells in colorectal carcinoma
    Bassorgun, C. I.
    Ozluk, A.
    Erin, N.
    Uzun, O. C.
    Elpek, G. O.
    VIRCHOWS ARCHIV, 2013, 463 (02) : 209 - 209
  • [29] S100A8 & S100A9: Alarmin mediated inflammation in tendinopathy
    Crowe, Lindsay A. N.
    McLean, Michael
    Kitson, Susan M.
    Melchor, Emma Garcia
    Patommel, Katharina
    Cao, Hai Man
    Reilly, James H.
    Leach, William J.
    Rooney, Brain P.
    Spencer, Simon J.
    Mullen, Michael
    Chambers, Max
    Murrell, George A. C.
    McInnes, Iain B.
    Akbar, Moeed
    Millar, Neal L.
    SCIENTIFIC REPORTS, 2019, 9 (1)
  • [30] S100A8 & S100A9: Alarmin Mediated Inflammation in Tendinopathy
    Crowe, Lindsay A. N.
    McLean, Michael
    Garcia-Melchor, Emma
    Patommel, Katharina
    Kitson, Susan M.
    Reilly, James H.
    McInnes, Iain B.
    Akbar, Moeed
    Millar, Neal L.
    ARTHRITIS & RHEUMATOLOGY, 2018, 70