Human cDNA encoding DnaJ protein homologue

Oh, Suwan; Iwahori, Akiyo; Kato, Souichiro

doi:10.1016/0167-4781(93)90104-l

Cited by 56 publications

(43 citation statements)

References 8 publications

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“…Our observation of increased association of Hsp9O with p6Ov-src in the ydjl-151 mutant, as well as co-immunoprecipitation of Ydjlp with p60v-src, provides further evidence for a role of Ydjlp in Hsp9O function, possibly via the action of Hsp7O as recently proposed (Caplan et al, 1995). Because Hsp9O-containing chaperone complexes are highly conserved in eukaryotes (Chang and Lindquist, 1994), it is to be expected that a homologue of Ydjlp has similar activities in vertebrate cells (Chellaiah et al, 1993;Oh et al, 1993).…”

Section: P60'src Is Produced In Normal Levels In a Ydjl Null Strainsupporting

confidence: 56%

The Ydj1 molecular chaperone facilitates formation of active p60v-src in yeast.

Dey

Caplan

Boschelli

1996

MBoC

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Molecular chaperones have been implicated in the formation of active p6ov-src tyrosine kinase. In Saccharomyces cerevisiae, expression of p60v-src causes cell death, a phenomenon that requires functional Hsp9O. We show here that mutations in a member of a second class of chaperones, the yeast dnaj homologue YDJ1, suppress the lethality caused by p6Ov-src. One p60v-src-resistant ydjl mutant, ydjl-39, which has two point mutations in the highly conserved "J" domain, has reduced levels of v-src mRNA and protein. However, a ydjl null mutant produces normal quantities of active p6Ov-src, indicating that Ydjlp facilitates, but is not essential for, the formation of active p6ov-src. We also report p60v-src_resistance in a previously identified temperature-sensitive ydjl mutant, ydjl-151. In this mutant, the level of p6oV-src remains unaltered, but the protein is much less active in vivo. In addition, p6Ovsrc immunoprecipitates from the ydjl-151 strain contained Hsp9O and Hsp7O in greater amounts than in wild-type strains. Ydjl protein was also detected in p60v-src immunoprecipitates from both wild-type and ydjl-151 strains. These results indicate that Ydjlp participates in the formation of active p60v-src via molecular chaperone complexes.

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Section: P60'src Is Produced In Normal Levels In a Ydjl Null Strainsupporting

confidence: 56%

The Ydj1 molecular chaperone facilitates formation of active p60v-src in yeast.

Dey

Caplan

Boschelli

1996

MBoC

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“…Figure 1A shows an alignment of the N termini of several polyomavirus TAgs including SV40 TAg and mouse polyomavirus TAg, with the J domains from several cellular DnaJ homologs, including E. coli DnaJ and two human homologs, DNAJ2 and HSJ1 (7,65). This alignment reveals several residues that are conserved between the TAgs and the DnaJ homologs.…”

Section: Resultsmentioning

confidence: 99%

“…The first exon of T (residues 1 to 82) was deleted, and the J domains from two different human DnaJ homologs, DNAJ2 (also known as HDJ-2 [9]) and HSJ1, was substituted. HSJ1 was isolated from a human brain expression library (7), and DNAJ2 was cloned from a human fibrosarcoma cell line (65). The amino-terminal 78 residues of HSJ1 or the amino-terminal 74 residues of DNAJ2 were fused to residues 83 to 708 of SV40 TAg.…”

Section: Resultsmentioning

confidence: 99%

Inactivation of pRB-Related Proteins p130 and p107 Mediated by the J Domain of Simian Virus 40 Large T Antigen

Stubdal

Zalvide

Campbell

et al. 1997

Molecular and Cellular Biology

171

198

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Inactivation of the retinoblastoma tumor suppressor protein (pRB) contributes to tumorigenesis in a wide variety of cancers. In contrast, the role of the two pRB-related proteins, p130 and p107, in oncogenic transformation is unclear. The LXCXE domain of simian virus 40 large T antigen (TAg) specifically binds to pRB, p107, and p130. We have previously shown that the N terminus and the LXCXE domain of TAg cooperate to alter the phosphorylation state of p130 and p107. Here, we demonstrate that TAg promotes the degradation of p130 and that the N terminus of TAg is required for this activity. The N terminus of TAg has homology to the J domain of the DnaJ family of molecular chaperone proteins. Mutants with mutations in the J-domain homology region of TAg are defective for altering p130 and p107 phosphorylation and for p130 degradation. A heterologous J-domain from a human DnaJ protein can functionally substitute for the N terminus of TAg in the effect on p107 and p130 phosphorylation and p130 stability. We further demonstrate that the J-domain homology region of TAg confers a growth advantage to wild-type mouse embryo fibroblasts (MEFs) but is dispensable in the case of MEFs lacking both p130 and p107. This indicates that p107 and p130 have overlapping growth-suppressing activities whose inactivation is mediated by the J domain of TAg.The retinoblastoma tumor suppressor gene (Rb-1) is mutated in all cases of retinoblastoma and is also frequently mutated in a variety of other cancers (55,91,92). Loss of the antiproliferative activity of the RB protein (pRB) is thought to play a critical role in oncogenic transformation. There are two other members of the RB family of proteins, p107 and p130. These proteins have a high degree of sequence homology to pRB (31,38,56,62). pRB, p107, and p130 share a number of functional properties, including the ability to associate with and negatively regulate members of the E2F family of transcription factors (3,6,8,36,42,78,89) and the ability to induce a G 1 arrest in certain sensitive cell types (16,43,103). The presence of a p130-E2F complex has been proposed to define a quiescent, or G 0 , state of a cell (80). pRB, p107, and p130 are phosphorylated in a cell cycle-dependent manner (2,4,10,21,61,96). Phosphorylation in the mid/late G 1 phase inactivates the growth-suppressive properties of pRB and possibly also of p107 and p130 (15,43,103). pRB, p107, and p130 associate with cyclins (28,30,32,38,47,54,56,78) and are likely to be phosphorylated by cyclin-dependent kinases (cdks). Despite all these similarities, no mutations in p107 or p130 have yet been described in human tumors, and the role of these two proteins in oncogenic transformation remains unclear. pRB appears to be an essential protein in mouse embryonic development, as mice with homozygous deletions of the Rb-1 gene die before birth (14, 46, 52). Moreover, mice heterozygous for Rb-1 develop pituitary tumors with a penetrance of almost 100% (40,45,46). In contrast, mice lacking either p107 or p130 apparently develop norm...

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“…The difference in cell lineages could influence the relations of chaperones, aggregation, and cell death. Although Hsdj we employed in this study is 99% identical to Hsdj2 employed in other reports at the level of amino acid sequence (32,44), the relationship between Hsdj and Hdj2 remains to be studied. Alternatively, ineffectiveness of Hsdj/Hdj2 in our study might be explained by relatively low overexpression of the protein in comparison with Hsp70 and/or Hsp40, as shown in Western blotting analysis.…”

Section: Discussionmentioning

confidence: 99%

Chaperones Hsp70 and Hsp40 Suppress Aggregate Formation and Apoptosis in Cultured Neuronal Cells Expressing Truncated Androgen Receptor Protein with Expanded Polyglutamine Tract

Kobayashi¹,

Kume²,

Li³

et al. 2000

Journal of Biological Chemistry

302

165

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Spinal and bulbar muscular atrophy (SBMA) is one of a group of human inherited neurodegenerative diseases caused by polyglutamine expansion. We have previously demonstrated that the SBMA gene product, the androgen receptor protein, is toxic and aggregates when truncated. Heat shock proteins function as molecular chaperones, which recognize and renaturate misfolded protein (aggregate). We thus assessed the effect of a variety of chaperones in a cultured neuronal cell model of SBMA. Overexpression of chaperones reduces aggregate formation and suppresses apoptosis in a cultured neuronal cell model of SBMA to differing degrees depending on the chaperones and their combinations. Combination of Hsp70 and Hsp40 was the most effective among the chaperones in reducing aggregate formation and providing cellular protection, reflecting that Hsp70 and Hsp40 act together in chaperoning mutant and disabled proteins. Although Hdj2/Hsdj chaperone has been previously reported to suppress expanded polyglutamine tract-formed aggregate, Hsdj/Hdj2 showed little effect in our system. These findings indicate that chaperones may be one of the key factors in the developing of CAG repeat disease and suggested that increasing expression level or enhancing the function of chaperones will provide an avenue for the treatment of CAG repeat disease.

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Human cDNA encoding DnaJ protein homologue

Cited by 56 publications

References 8 publications

The Ydj1 molecular chaperone facilitates formation of active p60v-src in yeast.

The Ydj1 molecular chaperone facilitates formation of active p60v-src in yeast.

Inactivation of pRB-Related Proteins p130 and p107 Mediated by the J Domain of Simian Virus 40 Large T Antigen

Chaperones Hsp70 and Hsp40 Suppress Aggregate Formation and Apoptosis in Cultured Neuronal Cells Expressing Truncated Androgen Receptor Protein with Expanded Polyglutamine Tract

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