Transglutaminase induction by various cell death and apoptosis pathways

Fésüs, László; Mádi, András; Balajthy, Zoltán; Nemes, Zoltán; Szondy, Zsuzsanna

doi:10.1007/bf01920102

Cited by 104 publications

(63 citation statements)

References 77 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Many reports have supported the involvement of TG2 in apoptosis. Its overexpression primes cells for suicide, and inhibition of its expression with an antisense strategy results in decreased cell death (21)(22)(23)(24). Nevertheless, expression of TG2 and apoptosis do not completely overlap.…”

Section: Discussionmentioning

confidence: 99%

Prognostic Significance of Tissue Transglutaminase in Drug Resistant and Metastatic Breast Cancer

Mehta

Fok

Miller

et al. 2004

Clinical Cancer Research

182

159

View full text Add to dashboard Cite

Purpose: Drug resistance and metastasis pose major impediments in the successful treatment of cancer. We previously reported that multidrug-resistant breast cancer cells exhibit high levels of tissue transglutaminase (TG2; EC 2.3.2.13). Because the drug-resistant and metastatic phenotypes are thought to share some common pathways, we sought to determine whether metastatic breast cancer cells express high levels of TG2.Experimental Design: The metastatic breast cancer cell line MDA-MB-231 and the sublines derived from it were tested for TG2 expression. Similarly, several sublines derived from an immortal but normal breast epithelial cell line, MCF10A, representing various stages in breast cancer progression were studied for TG2 expression. The primary and nodal tumor samples from 30 patients with breast cancer were also studied for TG2 expression.Results: The MDA-MB-231 cells expressed high basal levels of TG2. Two clones derived from this cell line, MDA231/cl.9 and MDA231/cl.16, showed a 10-to 15-fold difference in TG2 level. TG2-deficient MDA231/cl.9 cells exhibited higher sensitivity to doxorubicin and were less invasive than were the TG2-sufficient MDA231/cl.16 cells. The MCF10A-derived sublines had increased TG2 expression as they advanced from noninvasive to an invasive phenotype. Importantly, the metastatic lymph node tumors from patients with breast cancer showed significant higher levels of TG2 expression compared with the primary tumors from the same patients.Conclusions: TG2 expression is up-regulated in drugresistant and metastatic breast cancer cells, and it can serve as a valuable prognostic marker for these phenotypes.

show abstract

Section: Discussionmentioning

confidence: 99%

Prognostic Significance of Tissue Transglutaminase in Drug Resistant and Metastatic Breast Cancer

Mehta

Fok

Miller

et al. 2004

Clinical Cancer Research

182

159

View full text Add to dashboard Cite

show abstract

“…Activation of tTG by Serum Deprivation-tTG can be activated by a variety of external stimuli, including serum deprivation and retinoic acid (34,42). Thus, if the production of the stable core protein dimer were indeed due to tTG, then this production should also be enhanced by these stimuli in addition to calphostin C. For this reason, we tested whether serum deprivation would similarly enhance the production of the stable core protein dimer.…”

Section: Ttg Modification Of Hcv Core Proteinphostin C or Not (Data Nmentioning

confidence: 99%

Post-translational Modification of the Hepatitis C Virus Core Protein by Tissue Transglutaminase

Strohecker

2001

Journal of Biological Chemistry

View full text Add to dashboard Cite

The hepatitis C virus (HCV) core protein is a structural protein that packages the viral genomic RNA. In this study, we demonstrate that a stable core protein dimer could be produced in liver cells. The production of this protein could be enhanced by calphostin C and serum deprivation. This protein was determined to be the core protein dimer because of its reactivity with the anti-core antibody, its similar electrophoretic mobility compared with that of the core protein dimer generated by cross-linking with glutaraldehyde, and its increase in size by a hemagglutinin tag fused to the core protein sequence. This core protein dimer was highly stable and resistant to SDS and ␤-mercaptoethanol. The enzyme that mediated the formation of this stable core protein dimer was determined to be the tissue transglutaminase (tTG) because, first, tTG could be activated by calphostin C and serum deprivation; second, the formation of this dimer was suppressed by monodansylcadaverine, a tTG inhibitor; and third, the core protein could be crosslinked by tTG in vitro. Thus, the HCV core protein represents the first known viral structural protein substrate of tTG. The post-translational modification by tTG reduced the RNA binding activity of the core protein, raising the possibility that tTG may regulate the biological functions of the HCV core protein.

show abstract

“…During the years, it became clear that the enzyme overexpression occurred during phases of embryonic cell regression in organogenesis (e.g. in the foot interdigital membranes), that this same process could appear during regression after experimental induction of tissue hypertrophy (as proved by Laszlo Fesus in the liver of animals treated in vivo with lead salts) (Fesus et al 1987) and that in all these instances the death of the cells took place by apoptosis (Fesus et al 1991(Fesus et al , 1996. This link between transglutaminase 2 and programmed cell death has deeply influenced all successive transglutaminase research, including manipulation of transglutaminase expression for therapeutic goals, as occurred in the treatment of certain forms of leukemia (typically the promyelocytic leukemia, in which two cycles of treatment are effective in healing definitively over 85% of the patients) (Benedetti et al 1996;Ozpolat et al 2001;Asou 2007).…”

Section: The Years Of the Genementioning

confidence: 99%