Solution Structure of BID, an Intracellular Amplifier of Apoptotic Signaling

Chou, James J.; Li, Honglin; Salvesen, Guy S.; Yuan, Junying; Wagner, Gerhard

doi:10.1016/s0092-8674(00)80572-3

Cited by 443 publications

(410 citation statements)

References 44 publications

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“…28 The exception to this rule is BID, which is produced as an inactive globular protein that is converted into its active form, tBID (truncated BID), through caspase-8-mediated cleavage. 29,30 The BH3-only proteins are able to bind members of the BCL-2-like pro-survival subfamily and some of them can also bind to BAX and BAK, but there are substantial differences in their selectivity of interaction. 17 40 It remains unclear whether binding of BH3-only proteins to the pro-survival BCL-2-like proteins or their direct binding to BAX/BAK is more critical for the initiation of apoptosis.…”

Section: The Bcl-2-regulated Apoptotic Pathwaymentioning

confidence: 99%

The BCL-2 protein family, BH3-mimetics and cancer therapy

2015

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Escape from apoptosis is a key attribute of tumour cells and facilitates chemo-resistance. The 'BCL-2-regulated' or 'intrinsic' apoptotic pathway integrates stress and survival signalling to govern whether a cancer cell will live or die. Indeed, many pro-apoptotic members of the BCL-2 family have demonstrated tumour-suppression activity in mouse models of cancer and are lost or repressed in certain human cancers. Conversely, overexpression of pro-survival BCL-2 family members promotes tumorigenesis in humans and in mouse models. Many of the drugs currently used in the clinic mediate their therapeutic effects (at least in part) through the activation of the BCL-2-regulated apoptotic pathway. However, initiators of this apoptotic pathway, such as p53, are mutated, lost or silenced in many human cancers rendering them refractory to treatment. To counter such resistance mechanisms, a novel class of therapeutics, 'BH3-mimetics', has been developed. These drugs directly activate apoptosis by binding and inhibiting select antiapoptotic BCL-2 family members and thereby bypass the requirement for upstream initiators, such as p53. In this review, we discuss the role of the BCL-2 protein family in the development and treatment of cancer, with an emphasis on mechanistic studies using well-established mouse models of cancer, before describing the development and already recognised potential of the BH3-mimetic compounds.

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Section: The Bcl-2-regulated Apoptotic Pathwaymentioning

confidence: 99%

The BCL-2 protein family, BH3-mimetics and cancer therapy

2015

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“…Bim, Bad and Bmf are unstructured in the absence of a binding partner, and only their BH3 domain becomes structured upon binding a pro-survival protein (Hinds et al, 2007). In contrast, Bid shows a structure strikingly similar to that of Bax and Bcl-xL, even though it lacks recognizable BH1 and BH2 domains (Chou et al, 1999;McDonnell et al, 1999).…”

Section: The Bh3-only Proteinsmentioning

confidence: 99%

BH3-only proteins and their roles in programmed cell death

2008

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“…49,57,79,80,84 With an essential rule of engagement structurally defined, the mechanics of BCL-2 family interactions came into focus. On the proapoptotic side, NMR structures of BH3-only BID 85,86 and multidomain proapoptotic BAX 52 disclosed striking architectural similarities between the proponents and opponents of cell death (Figure 4c). BID and BAX likewise possess two central core helices that are surrounded by 6 or 7 amphipathic helices, respectively.…”

Section: Bcl-2 Family Form and Functionmentioning

confidence: 99%

BCL-2 in the crosshairs: tipping the balance of life and death

Walensky¹

2006

Cell Death Differ

225

175

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The discovery of B-cell lymphoma-2 (BCL-2) over 20 years ago revealed a new paradigm in cancer biology: the development and persistence of cancer can be driven by molecular roadblocks along the natural pathway to cell death. The subsequent identification of an expansive family of BCL-2 proteins provoked an intensive investigation of the interplay among these critical regulators of cell death. What emerged was a compelling tale of guardians and executioners, each participating in a molecular choreography that dictates cell fate. Ten years into the BCL-2 era, structural details defined how certain BCL-2 family proteins interact, and molecular targeting of the BCL-2 family has since become a pharmacological quest. Although many facets of BCL-2 family death signaling remain a mechanistic mystery, small molecules and peptides that effectively target BCL-2 are eliminating the roadblock to cell death, raising hopes for a medical breakthrough in cancer and other diseases of deregulated apoptosis.

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Solution Structure of BID, an Intracellular Amplifier of Apoptotic Signaling

Cited by 443 publications

References 44 publications

The BCL-2 protein family, BH3-mimetics and cancer therapy

The BCL-2 protein family, BH3-mimetics and cancer therapy

BH3-only proteins and their roles in programmed cell death

BCL-2 in the crosshairs: tipping the balance of life and death

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