Structure of Bcl-x
            <sub>L</sub>
            -Bak Peptide Complex: Recognition Between Regulators of Apoptosis

Sattler, Michael; Liang, Heng; Nettesheim, David G.; Meadows, Robert P.; Harlan, John E.; Eberstadt, Matthias; Yoon, Ho Sup; Shuker, Suzanne B.; Chang, Brian M.; Minn, Andy J.; Thompson, Craig B.; Fesik, Stephen W.

doi:10.1126/science.275.5302.983

Cited by 1,401 publications

(1,532 citation statements)

References 12 publications

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“…Furthermore, this peptide could inhibit the interaction between wild-type BAK and BCL-X L through competition. 101 These data are compatible with the…”

Section: Figuresupporting

confidence: 86%

“…Large arrows refer to amino acid residues in BH3 of BAK which interact with residues (small arrows) in the hydrophobic pocket (BH1-3) of BCL-XL. 101 and cell death regulation, although the contribution of the domains is different within different family members. BH1 to BH3 are conserved in all family members except BAD, whereas BH4 is only conserved in family members with antiapoptotic activity.…”

Section: Figurementioning

confidence: 99%

See 1 more Smart Citation

t(14;18), a journey to eternity

Meijerink

1997

Leukemia

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The t(14;18) is the most frequent chromosomal aberration observed in follicular non-Hodgkin's lymphoma (NHL), and less frequently in diffuse large cell lymphoma (DLCL). The t(14;18) does not affect overall survival in follicular NHL or DLCL. It provides a unique lymphoma-specific marker that can be used to quantify residual disease during treatment, and may forward evaluation of new treatment protocols. The t(14;18) results in the deregulation of bcl-2, a proto-oncogene that protects against induction of programmed cell death (PCD). Nowadays, a whole family of bcl-2-related genes has been identified and consist of members which can either protect or promote induction of PCD. The family members form protein dimers, and the relative abundance of specific dimers regulates the cellular sensitivity to death signals (the rheostat model). Aberrant expression of different family members in several types of malignancies alter the cellular rheostat and thereby promote cellular resistance to chemotherapy.

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“…Furthermore, this peptide could inhibit the interaction between wild-type BAK and BCL-X L through competition. 101 These data are compatible with the…”

Section: Figuresupporting

confidence: 86%

Section: Figurementioning

confidence: 99%

t(14;18), a journey to eternity

Meijerink

1997

Leukemia

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“…44 Interaction of the disordered BIM, BAD, BMF, BAK, and tBID with several pro-survival BCL-2 family members leads to the formation of an a-helical segment that anchors these BH3-only proteins to the hydrophobic groove of their binding partners. [45][46] In addition to BH3-only proteins shown in Figure 1, pro-survival BCL-2 family members include MCL-1, BFl-1, and BCB-B, all of which are expected to contain long functional IDPRs. 45 Overall, structural and sequence analyses revealed that many pro-apoptotic and pro-survival proteins of the BCL-2 family (which, in their turn, are tightly regulated by various PTMs among other means) are either IDPs or contain functionally important IDPRs.…”

Section: Discussionmentioning

confidence: 99%

“…[45][46] In addition to BH3-only proteins shown in Figure 1, pro-survival BCL-2 family members include MCL-1, BFl-1, and BCB-B, all of which are expected to contain long functional IDPRs. 45 Overall, structural and sequence analyses revealed that many pro-apoptotic and pro-survival proteins of the BCL-2 family (which, in their turn, are tightly regulated by various PTMs among other means) are either IDPs or contain functionally important IDPRs. 46 Furthermore, conformational plasticity and ability to fold upon binding were shown to have a crucial role in multifarious interactions of the BCL-2 family members with their numerous partners.…”

Section: Discussionmentioning

confidence: 99%

Resilience of death: intrinsic disorder in proteins involved in the programmed cell death

et al. 2013

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It is recognized now that intrinsically disordered proteins (IDPs), which do not have unique 3D structures as a whole or in noticeable parts, constitute a significant fraction of any given proteome. IDPs are characterized by an astonishing structural and functional diversity that defines their ability to be universal regulators of various cellular pathways. Programmed cell death (PCD) is one of the most intricate cellular processes where the cell uses specialized cellular machinery and intracellular programs to kill itself. This cell-suicide mechanism enables metazoans to control cell numbers and to eliminate cells that threaten the animal's survival. PCD includes several specific modules, such as apoptosis, autophagy, and programmed necrosis (necroptosis). These modules are not only tightly regulated but also intimately interconnected and are jointly controlled via a complex set of protein-protein interactions. To understand the role of the intrinsic disorder in controlling and regulating the PCD, several large sets of PCD-related proteins across 28 species were analyzed using a wide array of modern bioinformatics tools. This study indicates that the intrinsic disorder phenomenon has to be taken into consideration to generate a complete picture of the interconnected processes, pathways, and modules that determine the essence of the PCD. We demonstrate that proteins involved in regulation and execution of PCD possess substantial amount of intrinsic disorder. We annotate functional roles of disorder across and within apoptosis, autophagy, and necroptosis processes. Disordered regions are shown to be implemented in a number of crucial functions, such as protein-protein interactions, interactions with other partners including nucleic acids and other ligands, are enriched in post-translational modification sites, and are characterized by specific evolutionary patterns. We mapped the disorder into an integrated network of PCD pathways and into the interactomes of selected proteins that are involved in the p53-mediated apoptotic signaling pathway.

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“…These two pro-apoptotic proteins contain BH1-3 domains, and have a 3D structure very similar to that of the pro-survival members of the family (Sattler et al, 1997;Suzuki et al, 2000;Moldoveanu et al, 2006). Mice lacking Bax show mild lymphoid hyperplasia and male sterility because of sperm-cell differentiation defects (Knudson et al, 1995).…”

Section: Bax Bak and Bokmentioning

confidence: 99%