Mutations in the FUS gene cause amyotrophic lateral sclerosis (ALS-FUS). However, the exact pathogenic mechanism of mutant fused in sarcoma (FUS) protein is not completely understood. FUS is an RNA binding protein (RBP) localized predominantly in the nucleus, but ALS-linked FUS mutations can affect its nuclear localization signal impairing its impo...
Published in Plant physiology
The WEE1 and ATM AND RAD3-RELATED (ATR) kinases are important regulators of the plant intra-S-phase checkpoint; consequently, WEE1KO and ATRKO roots are hypersensitive to replication-inhibitory drugs. Here, we report on a loss-of-function mutant allele of the FASCIATA1 (FAS1) subunit of the chromatin assembly factor 1 (CAF-1) complex that suppresse...
Y The ataxia-telangiectasia mutated (ATM) and ATM and Rad3-related (ATR) kinases coordinate the DNA damage response. The roles described for Arabidopsis thaliana ATR and ATM are assumed to be conserved over other plant species, but molecular evidence is scarce. Here, we demonstrate that the functions of ATR and ATM are only partially conserved betw...
Klotho was first discovered as an anti-ageing protein linked to a number of age-related disease processes, including cardiovascular, renal, musculoskeletal, and neurodegenerative conditions. Emerging research has also demonstrated a potential therapeutic role for Klotho in cancer biology, which is perhaps unsurprising given that cancer and ageing s...
α-Synuclein (aSyn) toxicity is associated with cell cycle alterations, activation of DNA damage responses (DDR), and deregulation of autophagy. However, the relationships between these phenomena remain largely unknown. Here, we demonstrate that in a yeast model of aSyn toxicity and aging, aSyn expression induces Ras2-dependent growth signaling, cel...
The major impediment to effective cancer therapy has been the development of drug resistance. The tumour suppressive transcription factor FOXO3 promotes cell cycle arrest, senescence and cell death, and mediates the cytotoxic and cytostatic functions of cancer therapeutics. In consequence, FOXO3 is often downregulated as an adaptive response in can...
10.1186/s13045-019-0716-7 / JOURNAL OF HEMATOLOGY & ONCOLOGY / 12 / 1
Cellular senescence is now considered an important driving mechanism for chronic lung diseases, particularly COPD and idiopathic pulmonary fibrosis. Cellular senescence is due to replicative and stress-related senescence with activation of p53 and p16INK4a respectively, leading to activation of p21CIP1 and cell cycle arrest. Senescent cells secrete...
Published in Scientific Reports
Chemotherapy resistance is responsible for high mortality rates in neuroblastoma. MYCN, an oncogenic driver in neuroblastoma, controls pluripotency genes including LIN28B. We hypothesized that enhanced embryonic stem cell (ESC) gene regulatory programs could mark tumors with high pluripotency capacity and subsequently increased risk for therapy fai...
Expression of cyclin D1 is required for cancer cell survival and proliferation. This is presumably due to the role of cyclin D1 in RB inactivation. Here we investigated the prosurvival function of cyclin D1 in a number of cancer cell lines. We found that cyclin D1 depletion facilitated cellular senescence in several cancer cell lines tested. Senesc...
