We have been characterizing some of the genes from the
hsp70 multigene family. We have recently sequenced two additional members of this family. The
hsp70C gene is non-heat inducible and constitutively expressed, its mRNA is most abundant at the L1 larval stage. The
hsp70C protein shares a high degree of identity with the rat
grp78 protein (77% at the amino acid level). The rat
grp78 protein is related to the
hsp70 family and is found within the endoplasmic reticulum (Munro and Pelham, 1986, Cell 46, 291). The expression of the
grp78 gene is enhanced when the cell or organism is starved of glucose. The
hsp70C protein has a long, hydrophobic leader sequence and the COOH-terminal ER-retention signal sequence KDEL characteristic of the rat
grp78 protein. Therefore, we conclude that the
hsp70C gene is the
grp78 equivalent in C. elegans.In a comparison with the
hsp70C gene from C. briggsae, a high degree of homology in the coding and noncoding regions is observed. The 5' regulatory region of the two genes share several conserved blocks of sequences encompassing a heat shock element and copies of mammalian virus core enhancer sequences. One of these regions is highly conserved ( approximately 80%) with a sequence in the rat
grp78 regulatory region. This region in the rat
grp78 regulatory region is protected during nuclease footprinting studies (A. S. Lee, personal communication). We propose that this region may be involved in the glucose-mediated response. Another member of the
hsp70 family characterized is the highly heat inducible gene
hsp70D. We find that the
hsp70D gene is closely related to both the
hsp70C and
grp78 genes (76% and 71% at the amino acid level respectively). As such, we identify the
hsp70D gene as the first highly heat inducible variety of the
grp78 subfamily. The COOH- terminal sequence is HDEL and not KDEL found in the
hsp70C protein. Histidine is a conservative substitution of lysine and may function as an ER-retention signal. Only the last half of the
hsp70D gene has been sequenced so we are unable to determine if the
hsp70D gene, like the
hsp70C gene, has a long, hydrophobic leader sequence.