A Mitochondrial Protein, Bit1, Mediates Apoptosis Regulated by Integrins and Groucho/TLE Corepressors

Jan, Yiwen; Matter, Michelle L.; Pai, Jih‐Tung; Chen, Yen-Liang; Pilch, Ján; Komatsu, Masanobu; Ong, Edgar; Fukuda, Minoru; Ruoslahti, Erkki

doi:10.1016/j.cell.2005.07.022

Cited by 46 publications

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“…Jan et al 2 suggested that TLE1 is anti-apoptotic by showing that TLE1 counteracts the formation of the Bit1-AES complex, an atypical apoptotic pathway. However, TLE1 has not been correlated to the expression of apoptotic genes in other studies.…”

Section: Discussionmentioning

confidence: 99%

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The role of TLE1 in synovial sarcoma

Seo

Lee

et al. 2011

Journal Orthopaedic Research

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The treatment outcome of synovial sarcoma is poor owing to its resistance to radiation and chemotherapy. The Transducin-like Enhancer of Split 1 (TLE1) is a co-repressor that involves many signaling pathways like cell survival, hematopoiesis and differentiation. Although TLE1 is uniquely expressed in synovial sarcomas, the biological role of TLE1 is not completely understood. This study evaluated the function of TLE1 in synovial sarcomas using knock-down of TLE1, and examined whether the inhibition of TLE1 suppresses the proliferation of synovial sarcomas and enhances the cytotoxicity caused by doxorubicin (doxo). The over-expression of TLE1 was first confirmed in synovial sarcoma cells (HS-SYII). When the HS-SYII cells and normal fibroblast were transiently transfected with TLE1 siRNA, the MTT assay revealed growth inhibition in the HS-SY-11 cells but not in the normal fibroblast. TLE1 silencing also potentiated the cytotoxic effects of doxo against HS-SYII cells. This effect of TLE1 silencing was attributed mainly to the induction of apoptosis. Subsequent analysis revealed that Bcl-2 is a possible downstream target of TLE1 signaling. This study demonstrated that TLE1 is a critical factor for the survival of synovial sarcomas. Overall, the inhibition of TLE1 affects cell proliferation and the apoptosis pathway by suppressing the expression of Bcl-2.

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Section: Discussionmentioning

confidence: 99%

“…2,3 Human TLE1 operates with some critical transcription factors that regulate the survival, hematopoiesis and differentiation of normal cells. [4][5][6] TLE1 is expressed in synovial sarcomas, which is a unique factor that is barely expressed in other soft tissue tumors.…”

mentioning

confidence: 99%

The role of TLE1 in synovial sarcoma

Seo

Lee

et al. 2011

Journal Orthopaedic Research

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“…Interestingly, however, similar cell types often respond differently to the deprivation of ECM substrate, and tend to undergo programmed cell death with varying kinetics via differing mechanisms. 24,28 These studies suggested that the phenomenon was not actually a single death signal, but rather was a collection of different apoptotic cascades that were coordinately induced. Thus, anoikis occurs in any particular cell type in a manner dependent upon which apoptotic cascade is dominant in that cell.…”

Section: Anoikis: Apoptosis Due To the Lack Of Integrinmediated Survimentioning

confidence: 99%

Integrins as a distinct subtype of dependence receptors

Stupack

2005

Cell Death Differ

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In the absence of their cognate ligand, dependence receptors trigger programmed cell death. This function is the defining feature of dependence receptors, which include members of several different protein families. The integrins are a family of heterodimeric receptors for extracellular matrix (ECM) proteins, mediating cell anchorage and migration. Integrins share characteristics with dependence receptors, and integrin binding to substrate ECM ligands is essential for cell survival. Although integrins do not conform in all characteristics to the established definitions of dependence receptors, alterations in the expression of integrins and their ligands during physiological and pathological events, such as wound healing, angiogenesis and tumorigenesis, do regulate cell fate in a ligand-dependent manner. This biosensory function of integrins fits well with our current concept of dependence receptor action, and thus integrins may rightly be considered to comprise a distinct subclass of dependence receptor.

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“…Caspase-8 also contributes to adhesion-mediated resistance of U937 histiocytic lymphoma and Rosewell Park Memorial Institute medium (RPMI 8226) multiple myeloma cell lines by promoting c-Fas-associated death domain (FADD)-like interleukin-1-converting enzyme-like inhibitory protein-long binding to FADD protein (Shain et al, 2002). Interestingly, Jan et al (2004) showed caspase-independent anoikis involving a new protein called Bit1.…”

Section: Introductionmentioning

confidence: 99%

Integrin-linked kinase interacts with caspase-9 and -8 in an adhesion-dependent manner for promoting radiation-induced apoptosis in human leukemia cells

et al. 2006

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Integrin-mediated adhesion of leukemia cells to extracellular matrix proteins reduces apoptosis following radiation-induced genotoxic injury. To evaluate the role of integrin-linked kinase (ILK) in this process, HL60 human acute promyelocytic leukemia cells were stably transfected with ILK wild-type or kinase-hyperactive overexpression vectors. Suspension or fibronectin (FN) adhesion cultures were irradiated with X-rays and processed for measurement of apoptosis, mitochondrial transmembrane potential and caspase activation. Adhesion to FN pronouncedly reduced radiation-induced apoptosis of HL60 cells and vector controls. Intriguingly, overexpressed ILK enhanced apoptosis after irradiation by combined activation of caspase-3 through caspase-8 and -9 in irradiated FN cultures. Irradiation of ILK suspension cultures lacked caspase-8 activation, but showed serial cleavage of caspase-9, -3 and poly (ADPribose) polymerase. These findings further characterize the cell death-promoting function of ILK in DNAdamaged cells. Moreover, ILK might represent a potential therapeutic target for innovative chemo-and radiooncological approaches in hematological malignancies.

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A Mitochondrial Protein, Bit1, Mediates Apoptosis Regulated by Integrins and Groucho/TLE Corepressors

Abstract: Among its interests, the company has initiated various programs to produce vaccines for Plasmodium falciparum malaria and Plasmodium vivax malaria.

Cited by 46 publications

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The role of TLE1 in synovial sarcoma

The role of TLE1 in synovial sarcoma

Integrins as a distinct subtype of dependence receptors

Integrin-linked kinase interacts with caspase-9 and -8 in an adhesion-dependent manner for promoting radiation-induced apoptosis in human leukemia cells

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