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 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.
Department of Pathology and Harvard Center for Cancer Biology, Harvard Medical School, Boston, Massachusetts 02115, USA.
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Schilling
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De-Medina
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Syken
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Vidal
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Münger
D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D002460:Cell Line; D002874:Chromosome Mapping; D002885:Chromosomes, Human, Pair 16 / Q000235:genetics; D003001:Cloning, Molecular; D004330:Drosophila / Q000235:genetics; D029721:Drosophila Proteins; D005260:Female; D015870:Gene Expression; D016147:Genes, Tumor Suppressor; D050956:HSP40 Heat-Shock Proteins; D006360:Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D019476:Insect Proteins / Q000235:genetics / Q000378:metabolism; D008297:Male; D024101:Mitochondrial Proteins; D008969:Molecular Sequence Data; D009856:Oncogene Proteins, Viral / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D050725:Papillomavirus E7 Proteins; D011247:Pregnancy; D011485:Protein Binding; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D014018:Tissue Distribution
C093721:CG5504 protein, Drosophila; D029721:Drosophila Proteins; D050956:HSP40 Heat-Shock Proteins; D006360:Heat-Shock Proteins; D019476:Insect Proteins; D024101:Mitochondrial Proteins; D009856:Oncogene Proteins, Viral; D050725:Papillomavirus E7 Proteins; D012333:RNA, Messenger; C059731:oncogene protein E7, Human papillomavirus type 16