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

• Published in: Virology (New York, N.Y.) Vol. 247; no. 1; pp. 74 - 85
• Main Authors: Schilling, Boris, De-Medina, Tali, Syken, Josh, Vidal, Marc, Münger, Karl
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 20.07.1998
• Subjects: Amino Acid Sequence; Animals; Binding Sites; Cell Line; Chromosome Mapping; Chromosomes, Human, Pair 16 - genetics; Cloning, Molecular; Drosophila - genetics; Drosophila Proteins; Female; Gene Expression; Genes, Tumor Suppressor; Heat-Shock Proteins - genetics; Heat-Shock Proteins - metabolism; HSP40 Heat-Shock Proteins; Human papillomavirus; Humans; Insect Proteins - genetics; Insect Proteins - metabolism; Male; Molecular Sequence Data; Oncogene Proteins, Viral - chemistry; Oncogene Proteins, Viral - genetics; Oncogene Proteins, Viral - metabolism; Papillomavirus E7 Proteins; Pregnancy; Protein Binding; RNA, Messenger - genetics; RNA, Messenger - metabolism; Sequence Homology, Amino Acid; Tissue Distribution
• ISSN: 0042-6822; 1096-0341
• DOI: 10.1006/viro.1998.9220

We have cloned hTid-1, a human homolog of the Drosophila tumor suppressor protein Tid56, by virtue of its ability to form complexes with the human papillomavirus E7 oncoprotein. The carboxyl terminal cysteine-rich metal binding domain of E7 is the major determinant for interaction with hTid-1. The carboxyl terminus of E7 is essential for the functional and structural integrity of E7 and has previously been shown to function 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 HeLa 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. The large tumor antigens of polyomaviruses encode functional J-domains that are important for viral replication as well as cellular transformation. The ability of HPV E7 to interact with a cellular DnaJ protein suggests that these two viral oncoproteins may target common regulatory pathways through J-domains.