The human DnaJ protein, hTid-1, enhances binding of a multimer of the herpes simplex virus type 1 UL9 protein to ori
            <sub>s</sub>
            , an origin of viral DNA replication

Eom, Chi-Yong; Lehman, I. R.

doi:10.1073/pnas.042689499

Cited by 39 publications

(27 citation statements)

References 43 publications

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“…Although originally described as a prominent mitochondrial protein, hTid-1 has subsequently been shown to distribute in the cytoplasm and the nucleus as well (7,35). The interaction of hTid-1 with cytoplasmic, viral, and cellular factors supports a role for hTid-1 in the cytoplasm (7,14,35,36). Notably, a recent report demonstrated that a cytoplasmic variant of the l(2)tid gene product Tid47 plays a major role in tumor suppression in Drosophila (5).…”

Section: Discussionmentioning

confidence: 99%

“…hTid-1 also serves as the intracellular target for the viral transforming protein Tax from human T-cell leukemia virus type 1 (HTLV-1) and represses the Tax-induced transactivation of nuclear factor B (NF-B) (7,8). Subsequent studies demonstrated that hTid-1 interacts with the viral nuclear protein UL9 from herpes simplex virus type 1 (HSV-1) in enhancing the binding of UL9 to the viral genome to facilitate viral replication (14) and that hTid-1 forms a protein complex with Jak2 tyrosine kinase, adversely affecting its kinase activity (35).…”

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confidence: 99%

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Molecular Mechanism of hTid-1, the Human Homolog of Drosophila Tumor Suppressor l(2)Tid, in the Regulation of NF-κB Activity and Suppression of Tumor Growth

Cheng

Cenciarelli

Nelkin

et al. 2005

Molecular and Cellular Biology

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hTid-1, a human homolog of the Drosophila tumor suppressor l(2)Tid and a novel DnaJ protein, regulates the activity of nuclear factor B (NF-B), but its mechanism is not established. We report here that hTid-1 strongly associated with the cytoplasmic protein complex of NF-B-IB through direct interaction with IB␣/␤ and the IKK␣/␤ subunits of the IB kinase complex. These interactions resulted in suppression of the IKK activity in a J-domain-dependent fashion and led to the cytoplasmic retention and enhanced stability of IB. Overexpression of hTid-1 by using recombinant baculovirus or adenovirus led to inhibition of cell proliferation and induction of apoptosis of human osteosarcoma cells regardless of the p53 expression status. hTid-1 is a human homologue of the Drosophila tumor suppressor Tid56 encoded by the lethal(2)tumorous imaginal discs, or l(2)tid, gene (26). Loss of the l(2)tid gene causes malignancy of the anlagen of the adult organs, the imaginal discs in Drosophila (26). hTid-1 was initially identified as a cellular target for the viral oncogenic protein E7 derived from human papillomavirus type 16 (HPV16) (36). hTid-1 also serves as the intracellular target for the viral transforming protein Tax from human T-cell leukemia virus type 1 (HTLV-1) and represses the Tax-induced transactivation of nuclear factor B (NF-B) (7,8). Subsequent studies demonstrated that hTid-1 interacts with the viral nuclear protein UL9 from herpes simplex virus type 1 (HSV-1) in enhancing the binding of UL9 to the viral genome to facilitate viral replication (14) and that hTid-1 forms a protein complex with Jak2 tyrosine kinase, adversely affecting its kinase activity (35).The htid1 gene encodes two spliced variants of hTid-1, hTid-1 L , and hTid-1 S (37). The full-length hTid-1 L (long) comprises 480 amino acids, whereas hTid-1 S (short), generated via alternative splicing, produces a predicted protein of 453 amino acids that lacks the C-terminal 33 amino acids of hTid-1 L but contains an additional 6 amino acids (KRSTGN) (37). Aside from differences at the C termini, both hTid-1 variants share identical structural motifs, including an N-terminal mitochondria-processing signal peptide, an N-terminal conserved signature J domain, and a central cysteine-rich motif. hTid-1 was classified as a member of the DnaJ protein family and a molecular cochaperone based on its signature J domain and ability to interact with the heat shock protein 70 chaperone (Hsp70) (25,27). Currently, the biological functions of these two forms of hTid-1 are unclear. The two variants were reported to exhibit opposing effects on induction of apoptosis in the human osteosarcoma cell line U2OS in response to tumor necrosis factor-alpha (TNF-␣) and mitomycin C (37), but the mechanism by which hTid-1-mediated apoptosis and antiapoptosis is unknown. Whether hTid-1 functions as a human tumor suppressor is also unknown. The early reports that hTid-1 serves as an intracellular target for viral oncogenic proteins Tax and E7 suggest a role for hTid-1 as a tumor suppre...

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Molecular Mechanism of hTid-1, the Human Homolog of Drosophila Tumor Suppressor l(2)Tid, in the Regulation of NF-κB Activity and Suppression of Tumor Growth

Cheng

Cenciarelli

Nelkin

et al. 2005

Molecular and Cellular Biology

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“…Recently, Hsp40 and Hsp70 have also been reported to enhance the binding of UL9, the origin-binding protein of herpes simplex virus type 1, to oriS and the resultant ori opening (57). hTid-1, a human homolog of E. coli DnaJ, also binds to UL9 and promotes multimer formation from dimers (19). In addition, Hsp70 also interacts with Orc4p of Saccharomyces cerevisiae, dissociating the oligomerized Orc4p amino-terminal domain (23), a function which we previously proposed for Hsp70 in stimulating HPV-11 E1 binding to ori (34).…”

mentioning

confidence: 99%

Chaperone Proteins Abrogate Inhibition of the Human Papillomavirus (HPV) E1 Replicative Helicase by the HPV E2 Protein

Lin

Makhov

Griffith

et al. 2002

Molecular and Cellular Biology

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Human papillomavirus (HPV) DNA replication requires the viral origin recognition protein E2 and the presumptive viral replicative helicase E1. We now report for the first time efficient DNA unwinding by a purified HPV E1 protein. Unwinding depends on a supercoiled DNA substrate, topoisomerase I, singlestranded-DNA-binding protein, and ATP, but not an origin. Electron microscopy revealed completely unwound molecules. Intermediates contained two single-stranded loops emanating from a single protein complex, suggesting a bidirectional E1 helicase which translocated the flanking DNA in an inward direction. We showed that E2 protein partially inhibited DNA unwinding and that Hsp70 or Hsp40, which we reported previously to stimulate HPV-11 E1 binding to the origin and promote dihexameric E1 formation, apparently displaced E2 and abolished inhibition. Neither E2 nor chaperone proteins were detected in unwinding complexes. These results suggest that chaperones play important roles in the assembly and activation of a replicative helicase in higher eukaryotes. An E1 mutation in the ATP binding site caused deficient binding and unwinding of origin DNA, indicating the importance of ATP binding in efficient helicase assembly on the origin.Human and animal papillomaviruses are prevalent pathogens. Efficient origin (ori)-dependent replication of viral DNA requires the virus-encoded E1 and E2 proteins as well as cellular replication proteins (11,27,46,59,68). As such, these DNA viruses may serve as a model for higher eukaryotic DNA replication, as do simian virus 40 (SV40) and polyomavirus. The papillomavirus ori consists of several E2 binding sites (BS) flanking one E1 BS. E1 recruits the DNA polymerase ␣/primase (6, 12, 41) and the single-stranded-DNA-binding protein RPA (25). The human papillomavirus (HPV) E1 protein is required during initiation and elongation and is thought to be the replicative helicase (33). However, HPV E1 proteins are poor helicases in strand displacement assays (26, 65), and there has been no report of DNA-unwinding activity. In contrast, the bovine papillomavirus 1 (BPV-1) E1 exhibits helicase activity in both assays (51, 69).We previously reported that purified HPV-11 E1 protein expressed in insect Sf9 cells binds to ori with low affinity and specificity and also binds to DNA nonspecifically (33). Electron microscopy (EM) shows that E1 binds ori primarily as a hexamer and, at a low frequency, as a dihexamer (34). The human heat shock proteins Hsp70, Hdj2, and Hdj1 greatly stimulate E1 binding to ori. Hdj1 and Hdj2 encode members of the Hsp40 family of proteins that normally function as cochaperones of the Hsp70 proteins and greatly stimulate the ATPase activity of Hsp70 (for a review, see reference 21). However, in the case of the HPV-11 E1-ori association, their effects are independent and additive. Most strikingly, EM has revealed that Hsp40 but not Hsp70 promotes E1 dihexamer formation on ori (34). The BPV-1 E1 has been reported to be a hexameric helicase (48). However, EM revealed a bilobed comp...

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“…Recently, it was reported that eukaryotic DnaJ proteins (HDJ-1 and hTid-1) can significantly increase the association of UL9 with origin sequences (61,62). The mechanism by which this occurs is unclear but may involve dissagregation of UL9 as seen in DnaA-dependent initiation of E. coli replication from oriC or RepA-dependent initiation of plasmid P1 replication (63).…”

Section: Initiation Of Replicationmentioning

confidence: 99%

“…For example, the recent discovery that stress proteins modulate the originbinding activity of the HSV-1 initiator protein implicates their participation following reactivation due to stress (61,62). Similarly, the glucocorticoid response element in oriL may play a role in activating this origin during reactivation from latency (10).…”

Section: Latent Replicationmentioning

confidence: 99%

Herpes Virus Replication

Boehmer

Nimonkar

2003

IUBMB Life

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SummaryHerpesviruses are large double stranded DNA animal viruses with the distinguishing ability to establish latent, life-long infections. To date, eight human herpesviruses that exhibit distinct biological and corresponding pathological/clinical properties have been identified. During their life cycles, herpesviruses execute an intricate chain of events geared towards optimizing their replication. This sets an interesting paradigm to study fundamental biological processes. This review summarizes recent developments in herpesvirus research with emphasis on genome transactions, particularly with respect to the prototypic herpes simplex virus type-1. IUBMB Life, 55: 13-22, 2003

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The human DnaJ protein, hTid-1, enhances binding of a multimer of the herpes simplex virus type 1 UL9 protein to ori _s , an origin of viral DNA replication

Cited by 39 publications

References 43 publications

Molecular Mechanism of hTid-1, the Human Homolog of Drosophila Tumor Suppressor l(2)Tid, in the Regulation of NF-κB Activity and Suppression of Tumor Growth

Molecular Mechanism of hTid-1, the Human Homolog of Drosophila Tumor Suppressor l(2)Tid, in the Regulation of NF-κB Activity and Suppression of Tumor Growth

Chaperone Proteins Abrogate Inhibition of the Human Papillomavirus (HPV) E1 Replicative Helicase by the HPV E2 Protein

Herpes Virus Replication

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The human DnaJ protein, hTid-1, enhances binding of a multimer of the herpes simplex virus type 1 UL9 protein to ori s , an origin of viral DNA replication

Cited by 39 publications

References 43 publications

Molecular Mechanism of hTid-1, the Human Homolog of Drosophila Tumor Suppressor l(2)Tid, in the Regulation of NF-κB Activity and Suppression of Tumor Growth

Molecular Mechanism of hTid-1, the Human Homolog of Drosophila Tumor Suppressor l(2)Tid, in the Regulation of NF-κB Activity and Suppression of Tumor Growth

Chaperone Proteins Abrogate Inhibition of the Human Papillomavirus (HPV) E1 Replicative Helicase by the HPV E2 Protein

Herpes Virus Replication

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Product

Resources

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The human DnaJ protein, hTid-1, enhances binding of a multimer of the herpes simplex virus type 1 UL9 protein to ori _s , an origin of viral DNA replication