Human DNAJ in cancer and stem cells:
- Sterrenberg, Jason N, Edkins, Adrienne L, Blatch, Gregory L
- Authors: Sterrenberg, Jason N , Edkins, Adrienne L , Blatch, Gregory L
- Date: 2011
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/165118 , vital:41210 , DOI: 10.1016/j.canlet.2011.08.019
- Description: The heat shock protein 40 kDa (HSP40/DNAJ) co-chaperones constitute the largest and most diverse sub-group of the heat shock protein (HSP) family. DNAJ are widely accepted as regulators of HSP70 function, but also have roles as co-chaperones for the HSP90 chaperone machine, and a growing number of biological functions that may be independent of either of these chaperones. The DNAJ proteins are differentially expressed in human tissues and demonstrate the capacity to function to both promote and suppress cancer development by acting as chaperones for tumour suppressors or oncoproteins. We review the current literature on the function and expression of DNAJ in cancer, stem cells and cancer stem cells. Combining data from gene expression, proteomics and studies in other systems, we propose that DNAJ will be key regulators of cancer, stem cell and possibly cancer stem cell function. The diversity of DNAJ and their assorted roles in a range of biological functions means that selected DNAJ, provided there is limited redundancy and that a specific link to malignancy can be established, may yet provide an attractive target for specific and selective drug design for the development of anti-cancer treatments.
- Full Text:
- Date Issued: 2011
- Authors: Sterrenberg, Jason N , Edkins, Adrienne L , Blatch, Gregory L
- Date: 2011
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/165118 , vital:41210 , DOI: 10.1016/j.canlet.2011.08.019
- Description: The heat shock protein 40 kDa (HSP40/DNAJ) co-chaperones constitute the largest and most diverse sub-group of the heat shock protein (HSP) family. DNAJ are widely accepted as regulators of HSP70 function, but also have roles as co-chaperones for the HSP90 chaperone machine, and a growing number of biological functions that may be independent of either of these chaperones. The DNAJ proteins are differentially expressed in human tissues and demonstrate the capacity to function to both promote and suppress cancer development by acting as chaperones for tumour suppressors or oncoproteins. We review the current literature on the function and expression of DNAJ in cancer, stem cells and cancer stem cells. Combining data from gene expression, proteomics and studies in other systems, we propose that DNAJ will be key regulators of cancer, stem cell and possibly cancer stem cell function. The diversity of DNAJ and their assorted roles in a range of biological functions means that selected DNAJ, provided there is limited redundancy and that a specific link to malignancy can be established, may yet provide an attractive target for specific and selective drug design for the development of anti-cancer treatments.
- Full Text:
- Date Issued: 2011
Cancer stem cells in breast cancer and metastasis:
- Lawson, Jessica C, Blatch, Gregory L, Edkins, Adrienne L
- Authors: Lawson, Jessica C , Blatch, Gregory L , Edkins, Adrienne L
- Date: 2009
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/165057 , vital:41205 , DOI: 10.1007/s10549-009-0524-9
- Description: The cancer stem cell theory poses that cancers develop from a subset of malignant cells that possess stem cell characteristics and has been proposed to account for the development of a variety of malignancies, including breast cancer. These cancer stem cells (CSC) possess characteristics of both stem cells and cancer cells, in that they have the properties of self-renewal, asymmetric cell division, resistance to apoptosis, independent growth, tumourigenicity and metastatic potential. A CSC origin for breast cancer can neatly explain both the heterogeneity of breast cancers and the relapse of the tumours after treatment. However, many reports on CSC in the breast are contradictory. There is variation with respect to how breast cancer stem cells should be identified, their characteristics and a possible lack of correlation between clinical outcome and breast cancer stem cell status of a tumour. These combined factors have made breast cancer stem cells a highly contentious issue. In this review, we highlight the progress in the analysis of cancer stem cells, with an emphasis on breast cancer.
- Full Text:
- Date Issued: 2009
- Authors: Lawson, Jessica C , Blatch, Gregory L , Edkins, Adrienne L
- Date: 2009
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/165057 , vital:41205 , DOI: 10.1007/s10549-009-0524-9
- Description: The cancer stem cell theory poses that cancers develop from a subset of malignant cells that possess stem cell characteristics and has been proposed to account for the development of a variety of malignancies, including breast cancer. These cancer stem cells (CSC) possess characteristics of both stem cells and cancer cells, in that they have the properties of self-renewal, asymmetric cell division, resistance to apoptosis, independent growth, tumourigenicity and metastatic potential. A CSC origin for breast cancer can neatly explain both the heterogeneity of breast cancers and the relapse of the tumours after treatment. However, many reports on CSC in the breast are contradictory. There is variation with respect to how breast cancer stem cells should be identified, their characteristics and a possible lack of correlation between clinical outcome and breast cancer stem cell status of a tumour. These combined factors have made breast cancer stem cells a highly contentious issue. In this review, we highlight the progress in the analysis of cancer stem cells, with an emphasis on breast cancer.
- Full Text:
- Date Issued: 2009
A Trypanosoma cruzi heat shock protein 40 is able to stimulate the adenosine triphosphate hydrolysis activity of heat shock protein 70 and can substitute for a yeast heat shock protein 40
- Edkins, Adrienne L, Ludewig, M H, Blatch, Gregory L
- Authors: Edkins, Adrienne L , Ludewig, M H , Blatch, Gregory L
- Date: 2004
- Language: English
- Type: Article
- Identifier: vital:6465 , http://hdl.handle.net/10962/d1005794 , http://dx.doi.org/10.1016/j.biocel.2004.01.016
- Description: The process of assisted protein folding, characteristic of members of the heat shock protein 70 (Hsp70) and heat shock protein 40 (Hsp40) molecular chaperone families, is important for maintaining the structural integrity of cellular protein machinery under normal and stressful conditions. Hsp70 and Hsp40 cooperate to bind non-native protein conformations in a process of adenosine triphosphate (ATP)-regulated assisted protein folding. We have analysed the molecular chaperone activity of the cytoplasmic inducible Hsp70 from Trypanosoma cruzi (TcHsp70) and its interactions with its potential partner Hsp40s (T. cruzi DnaJ protein 1 [Tcj1] and T. cruzi DnaJ protein 2 [Tcj2]). Histidine-tagged TcHsp70 (His-TcHsp70), Tcj1 (Tcj1-His) and Tcj2 (His-Tcj2) were over-produced in Escherichia coli and purified by nickel affinity chromatography. The in vitro basal specific ATP hydrolysis activity (ATPase activity) of His-TcHsp70 was determined as 40 nmol phosphate/min/mg protein, significantly higher than that reported for other Hsp70s. The basal specific ATPase activity was stimulated to a maximal level of 60 nmol phosphate/min/mg protein in the presence of His-Tcj2 and a model substrate, reduced carboxymethylated α-lactalbumin. In vivo complementation assays showed that Tcj2 was able to overcome the temperature sensitivity of the ydj1 mutant Saccharomyces cerevisiae strain JJ160, suggesting that Tcj2 may be functionally equivalent to the yeast Hsp40 homologue (yeast DnaJ protein 1, Ydj1). These data suggest that Tcj2 is involved in cytoprotection in a similar fashion to Ydj1, and that TcHsp70 and Tcj2 may interact in a nucleotide-regulated process of chaperone-assisted protein folding.
- Full Text:
- Date Issued: 2004
- Authors: Edkins, Adrienne L , Ludewig, M H , Blatch, Gregory L
- Date: 2004
- Language: English
- Type: Article
- Identifier: vital:6465 , http://hdl.handle.net/10962/d1005794 , http://dx.doi.org/10.1016/j.biocel.2004.01.016
- Description: The process of assisted protein folding, characteristic of members of the heat shock protein 70 (Hsp70) and heat shock protein 40 (Hsp40) molecular chaperone families, is important for maintaining the structural integrity of cellular protein machinery under normal and stressful conditions. Hsp70 and Hsp40 cooperate to bind non-native protein conformations in a process of adenosine triphosphate (ATP)-regulated assisted protein folding. We have analysed the molecular chaperone activity of the cytoplasmic inducible Hsp70 from Trypanosoma cruzi (TcHsp70) and its interactions with its potential partner Hsp40s (T. cruzi DnaJ protein 1 [Tcj1] and T. cruzi DnaJ protein 2 [Tcj2]). Histidine-tagged TcHsp70 (His-TcHsp70), Tcj1 (Tcj1-His) and Tcj2 (His-Tcj2) were over-produced in Escherichia coli and purified by nickel affinity chromatography. The in vitro basal specific ATP hydrolysis activity (ATPase activity) of His-TcHsp70 was determined as 40 nmol phosphate/min/mg protein, significantly higher than that reported for other Hsp70s. The basal specific ATPase activity was stimulated to a maximal level of 60 nmol phosphate/min/mg protein in the presence of His-Tcj2 and a model substrate, reduced carboxymethylated α-lactalbumin. In vivo complementation assays showed that Tcj2 was able to overcome the temperature sensitivity of the ydj1 mutant Saccharomyces cerevisiae strain JJ160, suggesting that Tcj2 may be functionally equivalent to the yeast Hsp40 homologue (yeast DnaJ protein 1, Ydj1). These data suggest that Tcj2 is involved in cytoprotection in a similar fashion to Ydj1, and that TcHsp70 and Tcj2 may interact in a nucleotide-regulated process of chaperone-assisted protein folding.
- Full Text:
- Date Issued: 2004
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