bcl-x is expressed in embryonic and postnatal neural tissues and functions to prevent neuronal cell death.

González-Garcı́a, Maribel; García, Irene; Ding, Liang; O'Shea, Sue; Boise, Lawrence H.; Thompson, Craig B.; Núñez, Gabriel

doi:10.1073/pnas.92.10.4304

Cited by 253 publications

(155 citation statements)

References 24 publications

(28 reference statements)

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“…However, Bcl-2 becomes quickly downregulated in almost every neuronal population during development [38][39][40]. Since Bax expression is also maintained in mature neurons [41], our data support the idea that the Bcl-x L /Bax ratio might be one of the most important regulators of the response of neurons to TNF-α [40].…”

Section: Decreased Endogenous Bcl-x L Levels Render Pc12 Cells and Cosupporting

confidence: 76%

BCL-XL regulates TNF-α-mediated cell death independently of NF-κB, FLIP and IAPs

et al. 2008

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Section: Decreased Endogenous Bcl-x L Levels Render Pc12 Cells and Cosupporting

confidence: 76%

BCL-XL regulates TNF-α-mediated cell death independently of NF-κB, FLIP and IAPs

et al. 2008

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“…Some structural features (a domains) and functions determined by cristallographic or mutational analysis are indicated (Longo et al, 1997) Bcl-X L ; Mcl-1; A1 Prevent Bax/Bak-mediated killing (Manon et al, 1997;Sato et al, 1994;Tao et al, 1997) S. Pombe Bax Cell killing with chromatin condensation and vacuolization (Jurgensmeier et al, 1997) Bak Slow growth phenotype and killing with chromatic condensation and lamin dissolution (Ink et al, 1997;Jurgensmeier et al, 1997;Torgler et al, 1997) Bcl-X L , Bcl-2 Prevent Bax/Bak-mediated e ects (Jurgensmeier et al, 1997;Ink et al, 1997;Torgler et al, 1997) CED-4 Causes chromatin condenstaion and death CED-9 Prevents CED-4-induced death lular distribution of di erent members of the Bcl-2 family can depend on the cell type as well as on the family member. Thus, Bcl-2, Bcl-X L , Bax, and the Epstein ± Barr virus gene product BHRF tend to be particularly abundant in the outer mitochondrial membrane (Cory, 1995;Gonzalez-Garcia et al, 1994;Krajewski et al, 1993;Reed, 1994;Riparbelli et al, 1995;Yang and Korsmeyer, 1996;Zha et al, 1996a). In contrast, E1B19K, which lacks a TM domain, is mostly localized in the nuclear envelope (Rao et al, 1997).…”

Section: Predominant Localization To Intracellular Membranesmentioning

confidence: 99%

Subcellular and submitochondrial mode of action of Bcl-2-like oncoproteins

et al. 1998

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Bcl-2 is the prototype of a class of oncogenes which regulates apoptosis. Bcl-2-related gene products with either death-promoting and death-inhibitory activity are critically involved in numerous disease states and thus constitute prime targets for therapeutic interventions. The relative amount of death agonists and antagonists from the Bcl-2 family constitutes a regulatory rheostat whose function is determined, at least in part, by selective protein-protein interactions. Bcl-2 and its homologs insert into intracellular membranes including mitochondria, the endoplasmatic reticulum and the nuclear envelope. Many of the molecular genetic, ultrastructural, crystallographic and functional studies suggest that Bcl-2-related molecules exert their apoptosis-regulatory e ects via regulating mitochondrial alterations preceding the activation of apoptogenic proteases and nucleases. Via a direct e ect on mitochondrial membranes, Bcl-2 prevents all hallmarks of the early stage of apoptosis including disruption of the inner mitochondrial transmembrane potential and the release of apoptogenic protease activators from mitochondria. The mitochondrial permeability transition (PT) pore, also called mitochondrial megachannel or multiple conductance channel, is a multiprotein complex formed at the contact site between the mitochondrial inner and outer membranes, exactly at the same localization at which Bax, Bcl-2, and Bcl-X L are particularly abundant. The PT pore participates in the regulation of matrix Ca 2+ , pH, DC m , and volume and functions as a Ca 2+ -, voltage-, pH-, and redox-gated channel with several levels of conductance and little if any ion selectivity. Experiments involving the puri®ed PT pore complex indicate that Bax, Bcl-2, and Bcl-X L exert at least part of their apoptosis-regulatory function by facilitating (Bax) or inhibiting (Bcl-2, Bcl-X L ) PT pore opening. These ®ndings clarify the principal (but not exclusive) mechanism of Bcl-2-mediated cytoprotection.

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“…[11][12][13][14] More specifically, Bcl-X L is essential for neuronal survival during brain development and in the adult central nervous system (CNS) (knockout mice and gene-expression studies 15,16 ). In addition to its antiapoptotic role, recent studies have described new roles of Bcl-X L in cell physiology -effects on Ca 2 þ homeostasis and gene expression 17 and synaptic transmission regulation 18 -under not necessarily apoptotic conditions.…”

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confidence: 99%

Bcl-XL modulates the differentiation of immortalized human neural stem cells

et al. 2007

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Understanding basic processes of human neural stem cell (hNSC) biology and differentiation is crucial for the development of cell replacement therapies. Bcl-X L has been reported to enhance dopaminergic neuron generation from hNSCs and mouse embryonic stem cells. In this work, we wanted to study, at the cellular level, the effects that Bcl-X L may exert on cell death during differentiation of hNSCs, and also on cell fate decisions and differentiation. To this end, we have used both v-myc immortalized (hNS1 cell line) and non-immortalized neurosphere cultures of hNSCs. In culture, using different experimental settings, we have consistently found that Bcl-X L enhances neuron generation while precluding glia generation. These effects do not arise from a glia-to-neuron shift (changes in fate decisions taken by precursors) or by only cell death counteraction, but, rather, data point to Bcl-X L increasing proliferation of neuronal progenitors, and inhibiting the differentiation of glial precursors. In vivo, after transplantation into the aged rat striatum, Bcl-X L overexpressing hNS1 cells generated more neurons and less glia than the control ones, confirming the results obtained in vitro. These results indicate an action of Bcl-X L modulating hNSCs differentiation, and may be thus important for the future development of cell therapy strategies for the diseased mammalian brain. The efficient generation of human neurons and glia from stem cells is the object of intense investigation, in the context of basic and preclinical cell replacement research. 1,2 Different means of genetic and epigenetic manipulations of stem cell cultures are being tested, aiming at enhancing their ability to generate the desired cell types. [3][4][5][6] In previous studies, we and others have demonstrated that Bcl-X L overexpression has a major impact on the generation of dopaminergic neurons from human neural stem cells (hNSCs) and mouse embryonic stem cells (mES). 7,8 Also, recent data from conditional Bcl-X L mutant mice add support to these observations. 9,10 In the present study, we are extending these observations and analyzing in detail the effects of Bcl-X L on hNSCs differentiation, focusing on precursor cell fate choices, cell death, and precursor proliferation.Bcl-X L is the most potent antiapoptotic protein among Bcl-2 family members, both in vitro and in vivo. 11-14 More specifically, Bcl-X L is essential for neuronal survival during brain development and in the adult central nervous system (CNS) (knockout mice and gene-expression studies 15,16 ). In addition to its antiapoptotic role, recent studies have described new roles of Bcl-X L in cell physiology -effects on Ca 2 þ homeostasis and gene expression 17 and synaptic transmission regulation 18 -under not necessarily apoptotic conditions. Several other studies have also described the role of Bcl-X L in the control of cell cycle, 19,20 a process well known to be tightly linked to progression of precursor cells toward neuronal and glia differentiation. 21,22 In this work, we aimed...

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bcl-x is expressed in embryonic and postnatal neural tissues and functions to prevent neuronal cell death.

Abstract: Previous studies have implicated the bcl-2 protooncogene as a potential regulator of neuronal survival.

Cited by 253 publications

References 24 publications

BCL-XL regulates TNF-α-mediated cell death independently of NF-κB, FLIP and IAPs

BCL-XL regulates TNF-α-mediated cell death independently of NF-κB, FLIP and IAPs

Subcellular and submitochondrial mode of action of Bcl-2-like oncoproteins

Bcl-XL modulates the differentiation of immortalized human neural stem cells

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