NORE1A is a Ras-binding protein that belongs to a group of tumor suppressors known as the Ras association domain family. Their growth- and tumor-suppressive function is assumed to be dependent on association with the microtubule cytoskeleton. However, a detailed understanding of this interplay is still missing. Here, we show that NORE1A directly interacts with tubulin and is capable of nucleating microtubules. Strikingly, the ability to stimulate nucleation is regulated in a dual specific way either via phosphorylation of NORE1A within the Ras-binding domain by Aurora A kinase or via binding to activated Ras. We also demonstrate that NORE1A mediates a negative effect of activated Ras on microtubule nucleation. On the basis of our results, we propose a novel regulatory network composed of the tumor suppressor NORE1A, the mitotic kinase Aurora A, the small GTPase Ras, and the microtubule cytoskeleton.
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http://dx.doi.org/10.1074/jbc.M109.081562 | DOI Listing |
Nat Commun
December 2024
The SKI Stem Cell Research Facility, The Center for Stem Cell Biology and Developmental Biology Program, Sloan-Kettering Institute for Cancer Research, 1275 York Avenue, New York, NY, USA.
Prime editing (PE) allows for precise genome editing in human pluripotent stem cells (hPSCs), such as introducing single nucleotide modifications, small insertions or deletions at a specific genomic locus. Here, we systematically compare a panel of prime editing conditions in hPSCs and generate a potent prime editor, "PE-Plus", through co-inhibition of mismatch repair and p53-mediated cellular stress responses. We further establish an inducible prime editing platform in hPSCs by incorporating the PE-Plus into a safe-harbor locus and demonstrated temporal control of precise editing in both hPSCs and differentiated cells.
View Article and Find Full Text PDFJ Biomol Struct Dyn
February 2025
Laboratory of Integrative Genomics, Department of Integrative Biology, School of Bio Sciences and Technology, Vellore Institute of Technology (VIT), Vellore, India.
The P53 protein, a cancer-associated transcriptional factor and tumor suppressor, houses a Zn ion in its DNA-binding domain (DBD), essential for sequence-specific DNA binding. However, common mutations at position 273, specifically from Arginine to Histidine and Cysteine, lead to a loss of function as a tumor suppressor, also called DNA contact mutations. The mutant (MT) P53 structure cannot stabilize DNA due to inadequate interaction.
View Article and Find Full Text PDFFront Pediatr
December 2024
Department of Neurobiology, University of Alabama at Birmingham, Birmingham, AL, United States.
RHOBTB2 is a member of the Rho GTPases subfamily of signaling proteins, known tumor suppressors whose loss of function and decreased expression is associated with cancer onset. Beyond its cancer-related role, RHOBTB2 is implicated in rare neurodevelopmental disorders, specifically -related disorders, recognized in 2018 as a subtype of developmental and epileptic encephalopathies (DEE). Common symptoms of these disorders include early-onset epilepsy, severe intellectual disability, microcephaly, and movement disorders.
View Article and Find Full Text PDFNoncoding RNA Res
April 2025
Department of Cellular and Molecular Medicine, Herbert Wertheim College of Medicine, Florida International University, 11200 SW 8th Street, Miami, FL 33199, USA.
MicroRNAs (miRNAs) are classified as small, non-coding RNAs that play crucial roles in diverse biological processes, including cellular development, differentiation, growth, and metabolism. MiRNAs regulate gene expression by recognizing complementary sequences within messenger RNA (mRNA) molecules. Recent studies have revealed that miR-145-5p functions as a tumor suppressor in several cancers, including lung, liver, and breast cancers.
View Article and Find Full Text PDFGenes Dis
March 2025
The Mary & John Knight Translational Ovarian Cancer Research Unit, London Regional Cancer Program, London, ON N6A 4L6, Canada.
Genetic alterations to serine-threonine kinase 11 () have been implicated in Peutz-Jeghers syndrome and tumorigenesis. Further exploration of the context-specific roles of liver kinase B1 (LKB1; encoded by ) observed that it regulates AMP-activated protein kinase (AMPK) and AMPK-related kinases. Given that both migration and proliferation are enhanced with the loss of LKB1 activity combined with the prevalence of genetic alterations in cancer biopsies, LKB1 was marked as a tumor suppressor.
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