A NOVEL HUMAN DNAJ PROTEIN, HTID-1, A HOMOLOG OF THE DROSOPHILA TUMOR-SUPPRESSOR PROTEIN TID56, CAN INTERACT WITH THE HUMAN-PAPILLOMAVIRUS TYPE-16 E7 ONCOPROTEIN

We have cloned hTid-1, a human homolog of the Drosophila tumor suppres sor protein Tid56, by virtue of its ability to form complexes with the human papillomavirus E7 oncoprotein. The carboxyl terminal cysteine-r ich metal binding domain of E7 is the major determinant for interactio n with hTid-1. The carboxyl terminus of E7 is essential for the functi onal and structural integrity of E7 and has previously been shown to f unction as a multimerization domain. The hTid-1 protein is a member of the DnaJ-family of chaperones. Its mRNA is widely expressed in human tissues, including the HPV-18-positive cervical carcinoma cell line He La and human genital keratinocytes, the normal host cells of the HPVs. The hTid-1 gene has been mapped to the short arm of chromosome 16. Th e large tumor antigens of polyomaviruses encode functional J-domains t hat are important for viral replication as well as cellular transforma tion. The ability of HPV E7 to interact with a cellular DnaJ protein s uggests that these two viral oncoproteins may target common regulatory pathways through J-domains. (C) 1998 Academic Press.