The lincRNA JUNI regulates the stress-dependent induction of c-Jun, cellular migration and survival through the modulation of the DUSP14-JNK axis.

Cancer cells employ adaptive mechanisms to survive various stressors, including genotoxic drugs. Understanding the factors promoting survival is crucial for developing effective treatments. In this study, we unveil a previously unexplored long non-coding RNA, JUNI (JUN-DT, LINC01135), which is upregulated by genotoxic drugs through the activation of stress-activated MAPKs, JNK, and p38 and consequently exerts positive control over the expression of its adjacent gene product c-Jun, a well-known oncoprotein, which transduces signals to multiple transcriptional outputs.

Transcription factors bind negatively selected sites within human mtDNA genes.

Transcription of mitochondrial DNA (mtDNA)-encoded genes is thought to be regulated by a handful of dedicated transcription factors (TFs), suggesting that mtDNA genes are separately regulated from the nucleus. However, several TFs, with known nuclear activities, were found to bind mtDNA and regulate mitochondrial transcription. Additionally, mtDNA transcriptional regulatory elements, which were proved important in vitro, were harbored by a deletion that normally segregated among healthy individuals.

Differential regulation of FBXW7 isoforms by various stress stimuli.

Fbxw7 is a tumor suppressor mutated in a wide range of human cancers. It serves as the substrate recognition component of SCF E3 ubiquitin ligases, and intensive effort was made to identify its substrates. Some of the substrates are central regulators of the cell cycle, cell fate determination, and cellular survival.

Guidelines for the use and interpretation of assays for monitoring autophagy.

In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding.

Metalloprotease type III effectors that specifically cleave JNK and NF-κB.

Two major arms of the inflammatory response are the NF-κB and c-Jun N-terminal kinase (JNK) pathways. Here, we show that enteropathogenic Escherichia coli (EPEC) employs the type III secretion system to target these two signalling arms by injecting host cells with two effector proteins, NleC and NleD. We provide evidence that NleC and NleD are Zn-dependent endopeptidases that specifically clip and inactivate RelA (p65) and JNK, respectively, thus blocking NF-κB and AP-1 activation.

MDM2 and Fbw7 cooperate to induce p63 protein degradation following DNA damage and cell differentiation.

Tight control of p63 protein levels must be achieved under differentiation or apoptotic conditions. Here, we describe a new regulatory pathway for the DeltaNp63alpha protein. We found that MDM2 binds DeltaNp63alpha in the nucleus promoting its translocation to the cytoplasm.

Jun proteins inhibit autophagy and induce cell death.

Starvation induces a vigorous autophagic response to enhance cellular survival, whereas nutrient and serum supplementation inhibit autophagy and induce an intensive transcriptional burst that enables cellular proliferation. We recently found that some of the genes induced by serum and growth factors--the immediate early proteins JunB and c-Jun--inhibit autophagy. Deregulation of JunB expression when autophagy is specifically required, tilts the fate of starved cells to apoptosis.

Fumarase: a mitochondrial metabolic enzyme and a cytosolic/nuclear component of the DNA damage response.

In eukaryotes, fumarase (FH in human) is a well-known tricarboxylic-acid-cycle enzyme in the mitochondrial matrix. However, conserved from yeast to humans is a cytosolic isoenzyme of fumarase whose function in this compartment remains obscure. A few years ago, FH was surprisingly shown to underlie a tumor susceptibility syndrome, Hereditary Leiomyomatosis and Renal Cell Cancer (HLRCC).

Jun proteins are starvation-regulated inhibitors of autophagy.

The growing number of biological functions affected by autophagy ascribes a special significance to identification of factors regulating it. The activator protein-1 (AP-1) transcription factors are involved in most aspects of cellular proliferation, death, or survival, yet no information regarding their involvement in autophagy is available. Here, we show that the AP-1 proteins JunB and c-Jun, but not JunD, c-Fos, or Fra-1, inhibit autophagy.

AP-1--The Jun proteins: Oncogenes or tumor suppressors in disguise?

Since its discovery more than two decades ago the involvement of the Activating protein 1 (AP-1) in proliferation, inflammation, differentiation, apoptosis, cellular migration and wound healing has been intensively studied. A model based on the early studies suggested antagonistic roles for the Jun proteins in proliferation and transformation. c-Jun was suggested to enhance transformation whereas JunB suggested to inhibit it in an antagonistic manner.

DNA damage-dependent translocation of B23 and p19 ARF is regulated by the Jun N-terminal kinase pathway.

The dynamic behavior of the nucleolus plays a role in the detection of and response to DNA damage of cells. Two nucleolar proteins, p14(ARF)/p19(ARF) and B23, were shown to translocate out of the nucleolus after exposure of cells to DNA-damaging agents. This translocation affects multiple cellular functions, such as DNA repair, proliferation, and survival.

Transcriptional repression of c-Jun's E3 ubiquitin ligases contributes to c-Jun induction by UV.

UV radiation is a major environmental carcinogen. The oncoprotein c-Jun that is required for development of skin cancer is stabilized by UV radiation. The mechanism leading to its stabilization after exposure to UV is not known.

Induction of transcriptionally active Jun proteins regulates drug-induced senescence.

The drug hydroxyurea (HU) is used for cancer therapy and treatment of sickle cell anemia. It inhibits cell cycle progression by blocking DNA synthesis and drives cells to undergo apoptosis or enter senescence. We demonstrate here that HU induces the expression of two AP-1 proteins, c-Jun and JunB, which exert antagonistic effects on the cell cycle.

AP-1 as a regulator of cell life and death.

The transcription factor AP-1 (activator protein-1) is involved in cellular proliferation, transformation and death. Using mice and cells lacking AP-1 components, the target-genes and molecular mechanisms mediating these processes were recently identified. Interestingly, the growth-promoting activity of c-Jun is mediated by repression of tumour suppressors, as well as upregulation of positive cell cycle regulators.