The Yeast Sls1p and Fes1p Proteins Define a New Family of Hsp70 Nucleotide Exchange Factors

Title: The Yeast Sls1p and Fes1p Proteins Define a New Family of Hsp70 Nucleotide Exchange Factors

Volume: 4 Issue: 6

Author(s): Mehdi Kabani, Jean-Marie Beckerich and Jeffrey L. Brodsky

Affiliation:

Keywords: Yeast Sls1p, mitochondria, ER lumen, nucleotide

Abstract: Hsp70 molecular chaperones play a variety of functions in every organism, cell type and compartment, and their activities have been implicated in a number of disease states. Hsp70 activity relies on ATP binding and hydrolysis by the N-terminal domain, which modulates peptide binding and release by the C-terminal domain. In Escherichia coli, the Hsp70 family member DnaK is regulated by DnaJ, which stimulates its ATPase activity, and by GrpE, a nucleotide exchange factor that promotes ADP release. In eukaryotic cells, Hsp70 regulation is far more complex and many families of positive and negative regulators have been characterized, such as Bag-1 that was first identified as an anti-apoptotic Bcl2-binding protein. Whereas eukaryotic DnaJ homologs have extensively been studied, GrpE homolog are found only in the mitochondria or chloroplasts. In fact, until the discovery of Bag-1 in mammalian cells, nucleotide exchange factors were presumed absent from the eukaryotic cytosol and organelles that comprise the secretory pathway, such as the endoplasmic reticulum (ER). However, members of a novel class of nucleotide exchange factors in the ER and in the cytoplasm have recently been identified that act on the ER lumen and cytoplasmic Hsp70 proteins, respectively. Although first uncovered in yeast and named Sls1p and Fes1p, we report here that the class of Hsp70 nucleotide exchange factors defined by Sls1p and Fes1p is conserved from yeast to humans.

Cite this article as:

Kabani Mehdi, Beckerich Jean-Marie and Brodsky L. Jeffrey, The Yeast Sls1p and Fes1p Proteins Define a New Family of Hsp70 Nucleotide Exchange Factors, Current Genomics 2003; 4 (6) . https://dx.doi.org/10.2174/1389202033490268