Genome sequencing of pediatric medulloblastoma links catastrophic DNA rearrangements with TP53 mutations

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Highlights? Complex chromosomal alterations (chromothripsis) observed in medulloblastomas ? Cancers with such alterations harbor TP53 mutations ? Context-specific link between the status of p53 and likelihood of chromothripsis ? p53 status and chromothripsis also correlate with aggressive acute myeloid leukemia     

HMGB1-Facilitated p53 DNA Binding Occurs via HMG-Box/p53 Transactivation Domain Interaction,Regulated by the Acidic Tail

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Highlights? Binding of p53 to its cognate DNA is facilitated by HMGB1 ? The N-terminal region of p53 (residues 38–61; TAD2) interacts with the HMG boxes ? The acidic tail of HMGB1 masks the p53 binding site in the free proteins ? The structure of the A-box/p53(1–93) complex shows that TAD2 acts as an ss-DNA mimic     

c-MYC-Induced Sebaceous Gland Differentiation Is Controlled by an Androgen Receptor/p53 Axis

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Highlights? Myc-induced sebaceous differentiation depends on the androgen receptor and p53 ? The androgen receptor promotes sebocyte differentiation ? Myc induces a p53 response that promotes sebocyte proliferation ? p53 and the androgen receptor are mutually antagonistic     

Development and Regeneration of Sox2+ Endoderm Progenitors Are Regulated by a HDAC1/2-Bmp4/Rb1 Regulatory Pathway

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Highlights? Hdac1/2 regulate development of Sox2+ endoderm progenitors ? Bmp4, Rb1, p21, and p16 are direct targets of Hdac1/2 in lung endoderm ? Increased Bmp4 suppresses Sox2 expression in lung endoderm ? Hdac1/2 are required for lung secretory epithelial regeneration     

A Cell Cycle-Dependent Regulatory Circuit Composed of 53BP1-RIF1 and BRCA1-CtIP Controls DNA Repair Pathway Choice

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Highlights? 53BP1 inhibits BRCA1 recruitment to DSB sites in G1 ? RIF1 is the effector of 53BP1 during DSB repair ? Class-switch recombination requires RIF1 ? RIF1 recruitment to DSB sites in S/G2 is inhibited by BRCA1-CtIP     

RIF1 Is Essential for 53BP1-Dependent Nonhomologous End Joining and Suppression of DNA Double-Strand Break Resection

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Highlights? RIF1 is essential for 53BP1-dependent CSR and fusion of dysfunctional telomeres ? BRCA1 antagonizes RIF1 in S phase to prevent error-prone repair by toxic NHEJ ? N-terminal phospho-SQ/TQ domain of 53BP1 interacts with and recruits RIF1 to DSBs ? RIF1 and 53BP1 promote NHEJ in G1 by blocking 5′ end resection of DSBs     

Suppression of Host p53 Is Critical for Plasmodium Liver-Stage Infection

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Highlights? Protein lysate arrays are a useful tool for the study of host–pathogen interactions ? Hepatocyte signaling is substantially perturbed in response to Plasmodium infection ? Regulation of host p53 is required for efficient Plasmodium development ? Elevated levels of p53 eliminate Plasmodium parasites during the liver stage     

ZNF750 is a p63 target gene that induces KLF4 to drive terminal epidermal differentiation

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Highlights? Induction of ZNF750 expression is necessary for terminal epidermal differentiation ? The C2H2 domain of ZNF750 is necessary for its prodifferentiation function ? p63 is necessary for the induction of ZNF750 expression during differentiation ? ZNF750 activates the expression of KLF4 to drive differentiation gene expression     

Rspo3 binds syndecan 4 and induces Wnt/PCP signaling via clathrin-mediated endocytosis to promote morphogenesis

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Highlights? Discovery that Rspo3 binds syndecan 4 ? Rspo3/Sdc4 induce Wnt/PCP signaling via clathrin-mediated endocytosis ? Rspo3/PCP signaling is essential for gastrulation and cartilage morphogenesis     

Structure of lipid kinase p110β/p85β elucidates an unusual SH2-domain-mediated inhibitory mechanism

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Highlights? Both nSH2 and cSH2 domains of p85 inhibit basal activity of p110β ? p110β/p85β structure shows cSH2 contacts the C terminus of p110β ? Relief of cSH2 inhibition, unlike nSH2, requires extending beyond the pYXXM motif ? p110β C terminus is critical for phosphorylation of lipids and activation by RTKs     

An ERK-p38 Subnetwork Coordinates Host Cell Apoptosis and Necrosis during Coxsackievirus B3 Infection

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Highlights? Intracellular signaling predicts the fate of coxsackievirus B3 (CVB3)-infected cells ? p38 and ERK signaling pathways are tightly interconnected during CVB3 infection ? CVB3-induced apoptosis of cardiomyocytes is inhibited by ERK5 and ERK1/2 pathways ? CVB3 induces necrosis of cardiomyocytes via p38 activation     

The Structure of the Plk4 Cryptic Polo Box Reveals Two Tandem Polo Boxes Required for Centriole Duplication

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Highlights? The Plk4 cryptic polo box is a structurally unique, tandem polo box array: PB1-PB2 ? Full length Plk4 comprises three polo box domains, a unique polo kinase architecture ? The Plk4 PB1-PB2 cassette is required for Asterless binding and centriole targeting ? The Plk4 PB1-PB2 homodimer potentiates Plk4 degradation     

SIP1 Mediates Cell-Fate Decisions between Neuroectoderm and Mesendoderm in Human Pluripotent Stem Cells

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Highlights? Smad-interacting protein 1 (SIP1) regulates hESC differentiation ? SIP1 upregulation promotes neuroectodermal differentiation ? SIP1 inhibits mesendodermal and endodermal differentiation ? SMAD2/3 and NANOG/OCT4/SOX2 cooperatively regulate SIP1 expression     

Homologous Recombination DNA Repair Genes Play a Critical Role in Reprogramming to a Pluripotent State

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Highlights? Reprogramming increases the level of γH2AX, a marker of DNA DSBs ? Homologous recombination (HR) deficiency impairs reprogramming ? Reprogramming-induced DSBs and HR phenotypes are method-independent ? p53 deletion rescues reprogramming defects in HR-deficient cells     

ACTL6a Enforces the Epidermal Progenitor State by Suppressing SWI/SNF-Dependent Induction of KLF4

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Highlights? ACTL6a is downregulated during epidermal differentiation ? ACTL6a loss in epidermis causes progenitor loss and terminal differentiation ? ACTL6a is required for repression of KLF4 and other epidermal differentiation genes ? ACTL6a prevents binding of the SWI/SNF complex to differentiation genes     

Correction of both NBD1 energetics and domain interface is required to restore ΔF508 CFTR folding and function

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Highlights? NBD1 and NBD1-CL4 interface instability limit CFTR conformational maturation ? ΔF508 mutation thermodynamically and kinetically destabilizes NBD1 ? Stabilization of ΔF508-NBD1 is insufficient for CFTR-coupled domain folding ? ΔF508 CFTR folding and function require both NBD1 and NBD1-CL4 stabilization     

Cohesin-Dependent Association of Scc2/4 with the Centromere Initiates Pericentromeric Cohesion Establishment

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Highlights? Cohesin is required for the association of its loader, Scc2/4, with centromeres ? The Ctf19 kinetochore subcomplex targets the loader to centromeres ? Centromere-loaded cohesin ensures pericentromeric cohesion establishment ? Cohesin ring formation triggers cohesin loading via Scc2/4