Human homologue of murine tumor rejection antigen gp96: 5'-regulatory and coding regions and relationship to stress-induced proteins.

Maki, Robert G.; Old, Lloyd J.; Srivastava, Pramod K.

doi:10.1073/pnas.87.15.5658

Cited by 130 publications

(68 citation statements)

References 40 publications

(33 reference statements)

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“…Among these genes, we selected five targets reported to be involved in hyperthermia or oxidative cellular stress pathways, namely HSPA1B, HSP90B1, RAD51C, TIA1, and JUN (Maki et al 1990, Kyriakis et al 1994, Kedersha et al 2000, Qian et al 2006, Sage et al 2010. Moreover, all of these five genes have the putative binding sites of miR15a on the 3 0 -UTR.…”

Section: Regulation Of Hspa1b By Mir-15amentioning

confidence: 99%

Expressions of miR-15a and its target gene HSPA1B in the spermatozoa of patients with varicocele

Mou

et al. 2014

Reproduction

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Hyperthermia and oxidative stresses are the two central elements contributing to varicocele-related sperm damage. Growing evidence indicates that microRNAs (miRNAs) are involved in the regulation of the heat and oxidative stress responses. In this study, we analyzed the expressions of several stress-related miRNAs in the sperm and found that the expression of miR-15a was significantly decreased in patients with varicocele compared with the control. Furthermore, miR-15a repressed the expression of HSPA1B, which is a typical stressinduced chaperone protein, through directly binding its 3 0 -UTR. The expressions of miR-15a and HSPA1B exhibited an inverse correlation in sperm. Our results provide a valuable insight into the varicocele-related sperm impairment and male infertility, and may help to develop potential therapeutic targets and novel biomarkers for male infertility.

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Section: Regulation Of Hspa1b By Mir-15amentioning

confidence: 99%

Expressions of miR-15a and its target gene HSPA1B in the spermatozoa of patients with varicocele

Mou

et al. 2014

Reproduction

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“…Further studies on the downregulation of these genes in BT-549 cells followed by invasiveness assays may reveal their importance in this process. The significance of the other two genes that are down-regulated in MDA-MB-468 cells, namely the RNA helicase related protein [39] and the tumor rejection antigen (gp96) 1 [40], needs to be evaluated. We have validated the cytokeratin and metallothionein gene expression patterns in the non-invasive MCF7 breast cancer cells and highly aggressive MDA-MB-231 breast cancer cells (data not shown).…”

Section: Differential Expressions Of Genes In Bt-549 and Mda-mb-468 Cmentioning

confidence: 99%

Negative regulation of the expressions of cytokeratins 8 and 19 by SLUG repressor protein in human breast cells

Tripathi

Misra

Chaudhuri

2005

Biochemical and Biophysical Research Communications

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Invasiveness of tumor cells is often determined by the profile of their expressed genes. To determine the gene expression differences between an invasive and a non-invasive human breast tumor cells, we selected BT-549 (invasive) and MDA-MB-468 (non-invasive) cells, and compared their transcriptomes by cDNA microarray analysis. Among the significant differences in gene expressions, notable are the up-regulation of cytokeratins 8 and 19, and down-regulation of metallothioneins 1G and IL in MDA-MB-468 cells. Since MDA-MB-468 cells do not express SLUG, a member of a small family of E2-box-binding zinc finger silencer proteins, we studied whether the cytokeratin gene overexpressions in these cells are due to the absence of SLUG. Inducible expression of SLUG in MDA-MB-468 cells inhibited the expressions of the cytokeratin 8 and 19 but not others as was revealed by microarray analysis. Similarly, siRNA knock down of SLUG in BT-549 cells increased the expressions of those cytokeratin mRNAs. SLUG levels in the cell regulated the function of cytokeratins 8 and 19 gene promoters. We conclude that the expressions of cytokeratins and metallothioneins may be associated with the differential invasive behaviors of these breast tumor cells and SLUG may have regulatory roles in this process. KeywordsInvasiveness; Breast tumor; SLUG; Cytokeratin 8; Cytokeratin 19; Metallothionein 1G; Metallothionein 1L; siRNA; Microarray A serious gap in our understanding of cancer concerns malignancy and metastasis. We have yet to clearly identify gene defects that specifically permit cells to invade surrounding tissues, spread through the body, and form metastases. Local invasiveness requires a break down of the mechanisms that normally hold epithelial cells together. To determine the gene expression differences between an invasive and a non-invasive human breast tumor cells, we selected BT-549 (invasive) and MDA-MB-468 (non-invasive) cells, and compared their transcriptomes by cDNA microarray analysis. One of the known genotypic differences between these two cells is that BT-549 expresses the zinc finger repressor protein SLUG but the MDA-MB-468 cells do not [1]. Hence, we tested whether any gene overexpressed in the MDA-MB-468 cells is regulated by SLUG.We paid particular attention to SLUG because it is implicated as one of the determinants of tumor cell invasiveness [2][3][4][5][6]. This protein is a member of a superfamily of transcriptional regulators that are implicated in the formation of mesoderm and neural crest, as well as in We then overexpressed SLUG in MDA-MB-468 cells from a doxycycline-inducible promoter and compared the gene expression profile in the presence or absence of the inducer. We identified that cytokeratins 8 and 19 genes are repressed when SLUG expression is induced. We have verified the role of SLUG in regulating these cytokeratins by siRNA-mediated knock down of SLUG in BT-549 cells. We also report here our preliminary characterization of the promoters of these cytokeratin genes as it is regulated by SLUG exp...

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“…This finding indicated that Gln488 was indispensable for dimerization of Hsp90a. In fact, Gln488 is highly conserved in the Hsp90-family including yeast Hsp82 (Farrelly and Finkelstein 1984), yeast Hsc82 (Borkovich, et al 1989), human Grp94 (Maki, et al 1990), HtpG (Bardwell and Craig, 1987) and Drosophila melanogaster Trap1 (Felts, et al 2000).…”

Section: Dimeric Interaction Between MC Domains Having the Gln488his mentioning

confidence: 99%

Single Nucleotide Polymorphism that Accompanies a Missense Mutation (Gln488His) Impedes the Dimerization of Hsp90

et al. 2009

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3 Abstract A single nucleotide polymorphism (SNP) that causes a missense mutation of highly conserved Gln488 to His of the a isoform of the 90-kDa heat shock protein (Hsp90a) molecular chaperone is observed in Caucasians. The mutated Hsp90a severely reduced the growth of yeast cells. To investigate this molecular mechanism, we examined the domain-domain interactions of human Hsp90a by using bacterial 2-hybrid system. Hsp90a was expressed as a full-length form, N-terminal domain (residues 1-400), or middle (residues401-617) plus C-terminal (residues 618-732) domains (MC domain/amino acids 401-732). The Gln488His substitution in MC domain did not affect the intra-molecular interaction with N-terminal domain, whereas the dimeric interaction mediated by the inter-molecular interaction between MC domains was decreased to 32%. Gln488Ala caused a similar change, whereas Gln488Thr, which exceptionally occurs in mitochondrial Hsp90 paralog, fully maintained the dimeric interaction. Therefore, the SNP causing Gln488His mutation could abrogate the Hsp90 function due to reduced dimerization.

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Human homologue of murine tumor rejection antigen gp96: 5'-regulatory and coding regions and relationship to stress-induced proteins.

Abstract: Cell-surface glycoproteins of 96 kDa (gp96) have been implicated in immunogenicity of methylcholan-

Cited by 130 publications

References 40 publications

Expressions of miR-15a and its target gene HSPA1B in the spermatozoa of patients with varicocele

Expressions of miR-15a and its target gene HSPA1B in the spermatozoa of patients with varicocele

Negative regulation of the expressions of cytokeratins 8 and 19 by SLUG repressor protein in human breast cells

Single Nucleotide Polymorphism that Accompanies a Missense Mutation (Gln488His) Impedes the Dimerization of Hsp90

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