ERp29 – what does it do?

Project Details

The Endoplasmic Reticulum (ER) plays  several critical roles in cell biology including the production of secretory proteins and the safe storage of calcium inside cells. Numerous proteins reside  in the ER and so hold medical importance as potential therapeutic targets for  the many diseases associated with ER dysfunction (e.g. cystic fibrosis, type 2 diabetes, cancer). However, much needs to be learned about these ER residents  both in terms of their individual functions and how they work together as the  'ER machinery'. We discovered ERp29 during proteomic analysis of rat enamel  cells, leading to the naming and first description of this ubiquitous ER  resident in 1997. The challenge since has been to figure out the functional role of ERp29,  bioinformatics having offered only limited insight. In a series of pioneering  studies, we've gathered a variety of clues that collectively point to a novel  "housekeeping" role of general importance, probably as a new type of  chaperone. Now linked to a broad array of physiological processes and diseases  including cystic fibrosis and cancer, ERp29 holds broad potential as a medical target.

Researchers

Dr Jon Mangum, Project co-leader

Research Outcomes

  • Gorasia DG, Dudek NL, Safavi-Hemami H, Ayala Perez R, Schittenhelm RB, Saunders PM, Wee S, Mangum JE, Hubbard MJ, Purcell AW.  A prominent role of PDIA6 in processing of misfolded proinsulin. Biochim Biophys Acta 2016; 1864: 715-23. (PMID: 26947243)
  • Gorasia DG, Dudek NL, Veith PD, Shankar R, Safavi-Hermami H, Williamson NA, Reynolds EC, Hubbard MJ, Purcell AW.  Pancreatic beta cells are highly susceptible to oxidative and ER stresses during the development of diabetes.
    J Proteome Res 2015; 14: 688-99. (PMID: 25412008)
  • Suaud L, Miller K, Alvey L, Yan W, Robay A, Kebler C, Kreindler JL, Guttentag S, Hubbard MJ, Rubenstein RC. ERp29 Regulates {Delta}F508 and Wild-type Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) Trafficking to the Plasma Membrane in Cystic Fibrosis (CF) and Non-CF Epithelial Cells. J Biol  Chem 2011; 286: 21239-21253. (PMID: 21525008)
  • Das S, Smith TD, Sarma JD, Ritzenthaler JD, Maza J, Kaplan BE, Cunningham LA, Suaud L, Hubbard MJ, Rubenstein RC, Koval, M.  ERp29 restricts Connexin43 oligomerization in the endoplasmic reticulum. Mol Biol Cell 2009; 20: 2593-2604. (PMID: 19321666)
  • Shnyder SD, Mangum JE, Hubbard MJ. Triplex profiling of functionally distinct chaperones (ERp29/PDI/BiP) reveals marked heterogeneity of the endoplasmic reticulum proteome in cancer. J Proteome Res 2008; 7: 3364-3372. (PMID: 18598068)
  • Hermann VM, Cutfield JF, Hubbard MJ. Biophysical characterization of ERp29: evidence for a key structural role of Cysteine-125. J Biol Chem 2005; 280: 13529-13537. (PMID: 15572350)
  • Hubbard MJ, Mangum JE, McHugh NJ.  Purification and biochemical characterisation of native ERp29 from rat liver. Biochem J 2004; 383: 589-598. (PMID: 15500441)
  • Macleod JC, Sayer RJ, Lucocq JM, Hubbard MJ. ERp29, a general endoplasmic reticulum marker, is highly expressed throughout the brain. J Comp Neuro 2004; 477: 29-42.   (PMID: 15281078)
  • Shnyder SD, Hubbard MJ.  ERp29 is a ubiquitous resident of the endoplasmic reticulum with a distinct role in secretory protein production. J. Histochem Cytochem 2002; 50: 557-566 (PMID: 11897809)
  • Hubbard MJ.  Functional proteomics. The goalposts are moving. Proteomics 2002; 2: 1069-1078. (PMID: 12362325)
  • Hubbard MJ, McHugh NJ, Carne DL. Isolation of ERp29, a novel endoplasmic reticulum protein, from rat enamel cells: Evidence for a unique role in secretory-protein synthesis. Eur J  Biochem 2000: 267: 1945-1957. (PMID: 10727933)
  • Hubbard MJ, McHugh NJ. Human ERp29: Isolation, primary structural characterisation and two-dimensional gel mapping. Electrophoresis 2000; 21: 3785-379. (PMID: 11271497)
  • Demmer J, Zhou CM, Hubbard MJ. (1997) Molecular cloning of ERp29, a novel and widely expressed resident of the endoplasmic reticulum. FEBS Lett. 1997; 402, 145-150. (PMID: 9037184)

Research Group

Hubbard & Mangum laboratory: Proteomics and calcium biology



Faculty Research Themes

Child Health

School Research Themes

Molecular Mechanisms of Disease



Key Contact

For further information about this research, please contact the research group leader.

Department / Centre

Pharmacology and Therapeutics

Unit / Centre

Hubbard & Mangum laboratory: Proteomics and calcium biology