USP10 drives cancer stemness and enables super-competitor signalling in colorectal cancer.

The contribution of deubiquitylating enzymes (DUBs) to β-Catenin stabilization in intestinal stem cells and colorectal cancer (CRC) is poorly understood. Here, and by using an unbiassed screen, we discovered that the DUB USP10 stabilizes β-Catenin specifically in APC-truncated CRC in vitro and in vivo. Mechanistic studies, including in vitro binding together with computational modelling, revealed that USP10 binding to β-Catenin is mediated via the unstructured N-terminus of USP10 and is outcompeted by intact APC, favouring β-catenin degradation.

NEAT1 promotes genome stability via mA methylation-dependent regulation of CHD4.

Long noncoding (lnc)RNAs emerge as regulators of genome stability. The nuclear-enriched abundant transcript 1 (NEAT1) is overexpressed in many tumors and is responsive to genotoxic stress. However, the mechanism that links NEAT1 to DNA damage response (DDR) is unclear.

Association with TFIIIC limits MYCN localisation in hubs of active promoters and chromatin accumulation of non-phosphorylated RNA polymerase II.

MYC family oncoproteins regulate the expression of a large number of genes and broadly stimulate elongation by RNA polymerase II (RNAPII). While the factors that control the chromatin association of MYC proteins are well understood, much less is known about how interacting proteins mediate MYC's effects on transcription. Here, we show that TFIIIC, an architectural protein complex that controls the three-dimensional chromatin organisation at its target sites, binds directly to the amino-terminal transcriptional regulatory domain of MYCN.

PAF1c links S-phase progression to immune evasion and MYC function in pancreatic carcinoma.

In pancreatic ductal adenocarcinoma (PDAC), endogenous MYC is required for S-phase progression and escape from immune surveillance. Here we show that MYC in PDAC cells is needed for the recruitment of the PAF1c transcription elongation complex to RNA polymerase and that depletion of CTR9, a PAF1c subunit, enables long-term survival of PDAC-bearing mice. PAF1c is largely dispensable for normal proliferation and regulation of MYC target genes.

Nucleolar detention of NONO shields DNA double-strand breaks from aberrant transcripts.

RNA-binding proteins emerge as effectors of the DNA damage response (DDR). The multifunctional non-POU domain-containing octamer-binding protein NONO/p54nrb marks nuclear paraspeckles in unperturbed cells, but also undergoes re-localization to the nucleolus upon induction of DNA double-strand breaks (DSBs). However, NONO nucleolar re-localization is poorly understood.

Spt5 interacts genetically with Myc and is limiting for brain tumor growth in .

The transcription factor SPT5 physically interacts with MYC oncoproteins and is essential for efficient transcriptional activation of MYC targets in cultured cells. Here, we use to address the relevance of this interaction in a living organism. Spt5 displays moderate synergy with Myc in fast proliferating young imaginal disc cells.

MYC- and MIZ1-Dependent Vesicular Transport of Double-Strand RNA Controls Immune Evasion in Pancreatic Ductal Adenocarcinoma.

Deregulated expression of the MYC oncoprotein enables tumor cells to evade immune surveillance, but the mechanisms underlying this surveillance are poorly understood. We show here that endogenous MYC protects pancreatic ductal adenocarcinoma (PDAC) driven by KRAS and TP53 from eradication by the immune system. Deletion of TANK-binding kinase 1 (TBK1) bypassed the requirement for high MYC expression.

Combined inhibition of Aurora-A and ATR kinase results in regression of -amplified neuroblastoma.

Amplification of is the driving oncogene in a subset of high-risk neuroblastoma. The MYCN protein and the Aurora-A kinase form a complex during S phase that stabilizes MYCN. Here we show that MYCN activates Aurora-A on chromatin, which phosphorylates histone H3 at serine 10 in S phase, promotes the deposition of histone H3.

Ubiquitylation of MYC couples transcription elongation with double-strand break repair at active promoters.

The MYC oncoprotein globally affects the function of RNA polymerase II (RNAPII). The ability of MYC to promote transcription elongation depends on its ubiquitylation. Here, we show that MYC and PAF1c (polymerase II-associated factor 1 complex) interact directly and mutually enhance each other's association with active promoters.

MYC Recruits SPT5 to RNA Polymerase II to Promote Processive Transcription Elongation.

The MYC oncoprotein binds to promoter-proximal regions of virtually all transcribed genes and enhances RNA polymerase II (Pol II) function, but its precise mode of action is poorly understood. Using mass spectrometry of both MYC and Pol II complexes, we show here that MYC controls the assembly of Pol II with a small set of transcription elongation factors that includes SPT5, a subunit of the elongation factor DSIF. MYC directly binds SPT5, recruits SPT5 to promoters, and enables the CDK7-dependent transfer of SPT5 onto Pol II.

snoRNAs are a novel class of biologically relevant Myc targets.

Background: Myc proteins are essential regulators of animal growth during normal development, and their deregulation is one of the main driving factors of human malignancies. They function as transcription factors that (in vertebrates) control many growth- and proliferation-associated genes, and in some contexts contribute to global gene regulation.

Results: We combine chromatin immunoprecipitation-sequencing (ChIPseq) and RNAseq approaches in Drosophila tissue culture cells to identify a core set of less than 500 Myc target genes, whose salient function resides in the control of ribosome biogenesis.

Drosophila mbm is a nucleolar myc and casein kinase 2 target required for ribosome biogenesis and cell growth of central brain neuroblasts.

Proper cell growth is a prerequisite for maintaining repeated cell divisions. Cells need to translate information about intracellular nutrient availability and growth cues from energy-sensing organs into growth-promoting processes, such as sufficient supply with ribosomes for protein synthesis. Mutations in the mushroom body miniature (mbm) gene impair proliferation of neural progenitor cells (neuroblasts) in the central brain of Drosophila melanogaster.

Myc function in Drosophila.

Drosophila contains a single MYC gene. Like its vertebrate homologs, it encodes a transcription factor that activates many targets, including prominently genes involved in ribosome biogenesis and translation. This activity makes Myc a central regulator of growth and/or proliferation of many cell types, such as imaginal disc cells, polyploid cells, stem cells, and blood cells.

Myc Function in Drosophila.

Myc proteins control several cellular processes, including proliferation and growth, and they play an important role in human tumorigenesis. Several years ago, single homologs of Myc, its interaction partner Max, and its antagonist Mnt were identified in Drosophila melanogaster. Here, we review the function of this so-called Max network in fruit flies, with a particular emphasis on its most obvious biological activity: the control of cellular and organismal growth.

Drosophila Myc interacts with host cell factor (dHCF) to activate transcription and control growth.

The Myc proto-oncoproteins are transcription factors that recognize numerous target genes through hexameric DNA sequences called E-boxes. The mechanism by which they then activate the expression of these targets is still under debate. Here, we use an RNAi screen in Drosophila S2 cells to identify Drosophila host cell factor (dHCF) as a novel co-factor for Myc that is functionally required for the activation of a Myc-dependent reporter construct.

Flower dooms cells to death.

In Drosophila imaginal discs, viable cells are outcompeted by their faster growing neighbors in a process called "cell competition." A new study in this issue of Developmental Cell identifies the membrane protein Flower as being specifically induced in the outcompeted cells and required for their ensuing apoptosis.

Myc's secret life without Max.

The Myc transcription factors are amongst the most potent human oncoproteins, and they fulfill essential functions during normal development. Myc heterodimerizes with a protein called Max, and it has been widely assumed that all of Myc's activities depend on this association with Max. Recent evidence calls this view into question, as Myc proteins have been shown to retain considerable biological activity when not bound to Max.

Drosophila Myc.

Myc genes play a major role in human cancer, and they are important regulators of growth and proliferation during normal development. Despite intense study over the last three decades, many aspects of Myc function remain poorly understood. The identification of a single Myc homolog in the model organism Drosophila melanogaster more than 10 years ago has opened new possibilities for addressing these issues.

Max-independent functions of Myc in Drosophila melanogaster.

Myc proteins are powerful proto-oncoproteins and important promoters of growth and proliferation during normal development. They are thought to exercise their effects upon binding to their partner protein Max, and their activities are largely antagonized by complexes of Max with Mnt or an Mxd family protein. Although the biological functions of Myc, Mxd and Mnt have been intensively studied, comparatively little is known about the in vivo role of Max.

Getting started : an overview on raising and handling Drosophila.

Drosophila melanogaster has long been a prime model organism for developmental biologists. During their work, they have established a large collection of techniques and reagents. This in turn has made fruit flies an attractive system for many other biomedical researchers who have otherwise no background in fly biology.

Induction of apoptosis by Drosophila Myc.

Myc proteins are essential regulators of cellular growth and proliferation during normal development. Activating mutations in myc genes result in excessive growth and are frequently associated with human cancers. At the same time, forced expression of Myc sensitizes vertebrate cells towards different pro-apoptotic stimuli.

Control of transcription by Pontin and Reptin.

Pontin and Reptin are two closely related members of the AAA+ family of DNA helicases. They have roles in diverse cellular processes, including the response to DNA double-strand breaks and the control of gene expression. The two proteins share residence in different multiprotein complexes, such as the Tip60, Ino80, SRCAP and Uri1 complexes in animals, which are involved (directly or indirectly) in transcriptional regulation, but they also function independently from each other.