Novel Insights into the Post-translational Modifications of Ydj1/DNAJA1 Co-chaperones

Overview

Journal Cell Stress Chaperones

Publisher Elsevier

Specialty Cell Biology

Date 2024 Feb 3

PMID 38309209

Authors

Megan M Mitchem

Courtney Shrader

Elizabeth Abedi

Andrew W Truman

Affiliations

Soon will be listed here.

Abstract

The activity of the Hsp70 molecular chaperone is regulated by a suite of helper co-chaperones that include J-proteins. Studies on J-proteins have historically focused on their expression, localization, and activation of Hsp70. There is growing evidence that the post-translational modifications (PTMs) of chaperones (the chaperone code) fine-tune chaperone function. This mini-review summarizes the current understanding of the role and regulation of PTMs on the major J-proteins Ydj1 and DNAJA1. Understanding these PTMs may provide novel therapeutic avenues for targeting chaperone activity in cancer and neurodegenerative diseases.

Citing Articles

Acetylation of the yeast Hsp40 chaperone protein Ydj1 fine-tunes proteostasis and translational fidelity.

Omkar S, Mitchem M, Hoskins J, Shrader C, Kline J, Nitika PLoS Genet. 2024; 20(12):e1011338.

PMID: 39652584 PMC: 11658694. DOI: 10.1371/journal.pgen.1011338.

Pseudophosphorylation of single residues of the J-domain of DNAJA2 regulates the holding/folding balance of the Hsc70 system.

Velasco-Carneros L, Bernardo-Seisdedos G, Marechal J, Millet O, Moro F, Muga A Protein Sci. 2024; 33(8):e5105.

PMID: 39012012 PMC: 11249846. DOI: 10.1002/pro.5105.

Acetylation of the yeast Hsp40 chaperone protein Ydj1 fine-tunes proteostasis and translational fidelity.

Omkar S, Shrader C, Hoskins J, Kline J, Mitchem M, Nitika bioRxiv. 2024; .

PMID: 38915721 PMC: 11195281. DOI: 10.1101/2024.06.13.598777.

References

Walters R, Muhlrad D, Garcia J, Parker R . Differential effects of Ydj1 and Sis1 on Hsp70-mediated clearance of stress granules in Saccharomyces cerevisiae. RNA. 2015; 21(9):1660-71. PMC: 4536325. DOI: 10.1261/rna.053116.115. View

Fenyo D, Beavis R . The GPMDB REST interface. Bioinformatics. 2015; 31(12):2056-8. DOI: 10.1093/bioinformatics/btv107. View

Kampinga H, Craig E . The HSP70 chaperone machinery: J proteins as drivers of functional specificity. Nat Rev Mol Cell Biol. 2010; 11(8):579-92. PMC: 3003299. DOI: 10.1038/nrm2941. View

Li J, Sha B . Structure-based mutagenesis studies of the peptide substrate binding fragment of type I heat-shock protein 40. Biochem J. 2004; 386(Pt 3):453-60. PMC: 1134863. DOI: 10.1042/BJ20041050. View

Truman A, Kristjansdottir K, Wolfgeher D, Hasin N, Polier S, Zhang H . CDK-dependent Hsp70 Phosphorylation controls G1 cyclin abundance and cell-cycle progression. Cell. 2012; 151(6):1308-18. PMC: 3778871. DOI: 10.1016/j.cell.2012.10.051. View

Wright C, Fewell S, Sullivan M, Pipas J, Watkins S, Brodsky J . The Hsp40 molecular chaperone Ydj1p, along with the protein kinase C pathway, affects cell-wall integrity in the yeast Saccharomyces cerevisiae. Genetics. 2007; 175(4):1649-64. PMC: 1855118. DOI: 10.1534/genetics.106.066274. View

Fan C, Lee S, Cyr D . Mechanisms for regulation of Hsp70 function by Hsp40. Cell Stress Chaperones. 2004; 8(4):309-16. PMC: 514902. DOI: 10.1379/1466-1268(2003)008<0309:mfrohf>2.0.co;2. View

Craig E, Gambill B, Nelson R . Heat shock proteins: molecular chaperones of protein biogenesis. Microbiol Rev. 1993; 57(2):402-14. PMC: 372916. DOI: 10.1128/mr.57.2.402-414.1993. View

Ayala Mariscal S, Kirstein J . J-domain proteins interaction with neurodegenerative disease-related proteins. Exp Cell Res. 2021; 399(2):112491. DOI: 10.1016/j.yexcr.2021.112491. View

10.

Borges J, Fischer H, Craievich A, Ramos C . Low resolution structural study of two human HSP40 chaperones in solution. DJA1 from subfamily A and DJB4 from subfamily B have different quaternary structures. J Biol Chem. 2005; 280(14):13671-81. DOI: 10.1074/jbc.M408349200. View

11.

Tong X, Xu D, Mishra R, Jones R, Sun L, Schiltz G . Identification of a druggable protein-protein interaction site between mutant p53 and its stabilizing chaperone DNAJA1. J Biol Chem. 2020; 296:100098. PMC: 7948449. DOI: 10.1074/jbc.RA120.014749. View

12.

Omkar S, Truman A . Feeling the heat: how chaperones deal with biomolecular condensates. Trends Biochem Sci. 2022; 47(9):728-729. PMC: 9586463. DOI: 10.1016/j.tibs.2022.04.008. View

13.

Johnson J, Craig E . An essential role for the substrate-binding region of Hsp40s in Saccharomyces cerevisiae. J Cell Biol. 2001; 152(4):851-6. PMC: 2195774. DOI: 10.1083/jcb.152.4.851. View

14.

Jiang Y, Rossi P, Kalodimos C . Structural basis for client recognition and activity of Hsp40 chaperones. Science. 2019; 365(6459):1313-1319. PMC: 7023980. DOI: 10.1126/science.aax1280. View

15.

Walerych D, Olszewski M, Gutkowska M, Helwak A, Zylicz M, Zylicz A . Hsp70 molecular chaperones are required to support p53 tumor suppressor activity under stress conditions. Oncogene. 2009; 28(48):4284-94. DOI: 10.1038/onc.2009.281. View

16.

Aksnes H, Drazic A, Marie M, Arnesen T . First Things First: Vital Protein Marks by N-Terminal Acetyltransferases. Trends Biochem Sci. 2016; 41(9):746-760. DOI: 10.1016/j.tibs.2016.07.005. View

17.

Hildebrandt E, Cheng M, Zhao P, Kim J, Wells L, Schmidt W . A shunt pathway limits the CaaX processing of Hsp40 Ydj1p and regulates Ydj1p-dependent phenotypes. Elife. 2016; 5. PMC: 5014548. DOI: 10.7554/eLife.15899. View

18.

Backe S, Sager R, Woodford M, Makedon A, Mollapour M . Post-translational modifications of Hsp90 and translating the chaperone code. J Biol Chem. 2020; 295(32):11099-11117. PMC: 7415980. DOI: 10.1074/jbc.REV120.011833. View

19.

Moses M, Kim Y, Rivera-Marquez G, Oshima N, Watson M, Beebe K . Targeting the Hsp40/Hsp70 Chaperone Axis as a Novel Strategy to Treat Castration-Resistant Prostate Cancer. Cancer Res. 2018; 78(14):4022-4035. PMC: 6050126. DOI: 10.1158/0008-5472.CAN-17-3728. View

20.

Sojourner S, Graham W, Whitmore A, Miles J, Freeny D, Flores-Rozas H . The Role of HSP40 Conserved Motifs in the Response to Cytotoxic Stress. J Nat Sci. 2018; 4(4). PMC: 5906061. View