LHS1 encodes a non-essential protein with sequence similarity to the HSP70 family of molecular chaperones (5). HSP70 is a large family of proteins that has been evolutionarily conserved from bacteria (DnaK) to humans (HSP72/73). HSP70 proteins were originally classified based upon their induction by heat shock and their size of ~70kDa (reviewed in 6). S. cerevisiae has at least 9 cytosolic forms of HSP70 (encoded by SSA1, SSA2, SSA3, SSA4, SSB1, SSB2, SSE1, SSE2, SSZ1), 2 HSP70s which are found in the endoplasmic reticulum (KAR2, LHS1), and 3 mitochondrial HSP70 proteins (SSC1, SSQ1, ECM10).

Lhs1p localizes to the ER and shares 24% amino acid identity with the other ER HSP70 protein, Kar2p (1). These two proteins reciprocally regulate each other; the ATPase activity of Lhs1p is stimulated by Kar2p and Lhs1p enhances the rate of Kar2p ATP turnover by providing specific nucleotide exchange (4). While Kar2p is involved in both co- and post-translational targeting of proteins into the ER, Lhs1p only participates in post-translational import (3). In addition, Lhs1p activity also affects the refolding and stability of heat-denatured proteins (7).

LHS1 expression is induced by the drug tunicamycin and also by conditions that lead to the accumulation of unfolded proteins and triggering of the Unfolded Protein Response (UPR) (1, 2). Upregulation of LHS1 expression during UPR is mediated by the transcriptional activator Hac1p, which binds a 22 base pair UPR element, containing the consensus sequence 5'-CAGCGTG-3', present in the LHS1 promoter (8, 1). lhs1 null mutations result in cold sensitivity, enhanced resistance to manganese, a partial block in ER protein translocation, and constitutive activation of UPR (1, 2).

Last updated: 2006-02-12