Molecular Regulation of Human Cathepsin B: Implication in Pathologies

Yan, Shaohua; Sloane, Bonnie F.

doi:10.1515/bc.2003.095

Cited by 121 publications

(84 citation statements)

References 62 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…6A). The HDI-alb Ø induced cathepsin B protein differed in size from the lysosomally-processed fully mature form 37 found in control cultures (Fig. 6A), supporting the gene expression and cytology data (above) suggestive of altered lysosomal activity.…”

Section: Isocyanate-albumin Induced Changes In Cellular Proteinssupporting

confidence: 82%

Human innate immune responses to hexamethylene diisocyanate (HDI) and HDI–albumin conjugates

Wisnewski

Liu

et al. 2008

Clin Experimental Allergy

View full text Add to dashboard Cite

show abstract

Section: Isocyanate-albumin Induced Changes In Cellular Proteinssupporting

confidence: 82%

Human innate immune responses to hexamethylene diisocyanate (HDI) and HDI–albumin conjugates

Wisnewski

Liu

et al. 2008

Clin Experimental Allergy

View full text Add to dashboard Cite

show abstract

“…Numerous studies have shown that Ctsb and other cathepsins can function in degrading the extracellular matrix (ECM) in association with multiple processes, including endothelial tube formation (Cavallo-Medved et al, 2009), tumor cell progression (Bengsch et al, 2013;Buck et al, 1992;Koblinski et al, 2002;Porter et al, 2013;Turk et al, 2000;Yan and Sloane, 2003) and rheumatoid arthritis (Hashimoto et al, 2001). The ECM components fibronectin and laminin are first evident at 65% epiboly in zebrafish embryos (Latimer and Jessen, 2010), which is a stage after we first observed defects in split top mutants, suggesting that ECM degradation is not an essential maternal function of Ctsba.…”

Section: Discussion Ctsba Endopeptidase Function In Developmentmentioning

confidence: 82%

Split top: A maternal cathepsin B that regulates dorsoventral patterning and morphogenesis

et al. 2016

View full text Add to dashboard Cite

The vertebrate embryonic dorsoventral axis is established and patterned by Wnt and bone morphogenetic protein (BMP) signaling pathways, respectively. Whereas Wnt signaling establishes the dorsal side of the embryo and induces the dorsal organizer, a BMP signaling gradient patterns tissues along the dorsoventral axis. Early Wnt signaling is provided maternally, whereas BMP ligand expression in the zebrafish is zygotic, but regulated by maternal factors. Concomitant with BMP activity patterning dorsoventral axial tissues, the embryo also undergoes dramatic morphogenetic processes, including the cell movements of gastrulation, epiboly and dorsal convergence. Although the zygotic regulation of these cell migration processes is increasingly understood, far less is known of the maternal regulators of these processes. Similarly, the maternal regulation of dorsoventral patterning, and in particular the maternal control of ventral tissue specification, is poorly understood. We identified split top, a recessive maternal-effect zebrafish mutant that disrupts embryonic patterning upstream of endogenous BMP signaling. Embryos from split top mutant females exhibit a dorsalized embryonic axis, which can be rescued by BMP misexpression or by derepressing endogenous BMP signaling. In addition to dorsoventral patterning defects, split top mutants display morphogenesis defects that are both BMP dependent and independent. These morphogenesis defects include incomplete dorsal convergence, delayed epiboly progression and an early lysis phenotype during gastrula stages. The latter two morphogenesis defects are associated with disruption of the actin and microtubule cytoskeleton within the yolk cell and defects in the outer enveloping cell layer, which are both known mediators of epiboly movements. Through chromosomal mapping and RNA sequencing analysis, we identified the lysosomal endopeptidase cathepsin Ba (ctsba) as the gene deficient in split top embryos. Our results identify a novel role for Ctsba in morphogenesis and expand our understanding of the maternal regulation of dorsoventral patterning.

show abstract

“…This class of proteases is capable of degrading extracellular matrix components (20)(21)(22); thus, cysteine proteases have long been considered of potential importance during tumor cell invasion and metastasis (55,56). Cystatin M is a secreted protein and, when expressed at appropriate levels, functions to constrain extracellular cysteine protease activity (27).…”

Section: Discussionmentioning

confidence: 99%

Epigenetic Silencing of the Tumor Suppressor Cystatin M Occurs during Breast Cancer Progression

Kim

et al. 2006

Cancer Research

View full text Add to dashboard Cite

Cystatin M is a secreted inhibitor of lysosomal cysteine proteases. Several lines of evidence indicate that cystatin M is a tumor suppressor important in breast malignancy; however, the mechanism(s) that leads to inactivation of cystatin M during cancer progression is unknown. Inspection of the human cystatin M locus uncovered a large and dense CpG island within the 5 ¶ region of this gene (termed CST6). Analysis of cultured human breast tumor lines indicated that cystatin M expression is either undetectable or in low abundance in several lines; however, enhanced gene expression was measured in cells cultured on the DNA demethylating agent 5-aza-2 ¶-deoxycytidine (5-aza-dC). Increased cystatin M expression does not correlate with a cytotoxic response to 5-aza-dC; rather, various molecular approaches indicated that the CST6 gene was aberrantly methylated in these tumor lines as well as in primary breast tumors. Moreover, 60% (12 of 20) of primary tumors analyzed displayed CST6 hypermethylation, indicating that this aberrant characteristic is common in breast malignancies. Finally, preinvasive and invasive breast tumor cells were microdissected from nine archival breast cancer specimens. Of the five tumors displaying CST6 gene methylation, four tumors displayed methylation in both ductal carcinoma in situ and invasive breast carcinoma lesions and reduced expression of cystatin M in these tumors was confirmed by immunohistochemistry. In summary, this study establishes that the tumor suppressor cystatin M is a novel target for epigenetic silencing during mammary tumorigenesis and that this aberrant event can occur before development of invasive breast cancer. (Cancer Res 2006; 66(16): 7899-909)

show abstract

Molecular Regulation of Human Cathepsin B: Implication in Pathologies

Cited by 121 publications

References 62 publications

Human innate immune responses to hexamethylene diisocyanate (HDI) and HDI–albumin conjugates

Human innate immune responses to hexamethylene diisocyanate (HDI) and HDI–albumin conjugates

Split top: A maternal cathepsin B that regulates dorsoventral patterning and morphogenesis

Epigenetic Silencing of the Tumor Suppressor Cystatin M Occurs during Breast Cancer Progression

Contact Info

Product

Resources

About