Cancer Biology Research’s Post

Specific internal signals trigger events in the cell cycle👇 📎Progress through the cell cycle depends on the activities of cyclin-dependent kinases, or CDKs. We know that a protein kinase is an enzyme that catalyzes the transfer of a phosphate group from ATP to a target protein; this phosphate transfer is called phosphorylation. A particular CDK controls the G1-to-S transition, which is a control point in the cell cycle called the restriction point (R). Other CDKs control other parts of the cell cycle. 📎CDKs are not enzymatically active as protein kinases unless they are bound to another class of protein, the activators called cyclins. The binding of its cyclin—an example of allosteric regulation—activates the CDK by altering its shape and exposing its active site to substrates. The cyclin–CDK that controls passage from G1 to S phase is not the only such complex involved in regulating the eukaryotic cell cycle. There are different cyclin–CDK complexes, composed of particular cyclins and their associated CDKs, that act at different stages of the cycle. The details of how these complexes form and function vary among eukaryotic organisms, but we will focus here on the complexes found in mammalian cells. As an example, let’s take a closer look at the cyclin–CDK complex that controls the G1-to-S transition. 📎Binding of a cyclin changes the three-dimensional structure of an inactive CDK, making it an active protein kinase. Each cyclin–CDK complex phosphorylates a specific target protein in the cell cycle.

✨P4 ATPases (i.e., lipid flippases) are eukaryotic enzymes that transport lipids across membrane bilayers. In plants, P4 ATPases are named Aminophospholipid ATPases (ALAs) and are organized into five phylogenetic clusters. ⚒️Here, authors generated an Arabidopsis mutant lacking all five cluster-2 ALAs (ala8/9/10/11/12), which is the most highly expressed ALA subgroup in vegetative tissues. 📊 Plants harboring the quintuple knockout (KO) show rosettes that are 2.2-fold smaller and display chlorotic lesions. A similar but less severe phenotype was observed in an ala10/11 double KO. The growth and lesion phenotypes of ala8/9/10/11/12 mutants were reversed by expressing a NahG transgene, which encodes an enzyme that degrades salicylic acid (SA). 🩹A role for SA in promoting the lesion phenotype was further supported by quantitative PCR assays showing increased mRNA abundance for an SA-biosynthesis gene ISOCHORISMATE SYNTHASE 1 (ICS1) and two SA-responsive genes PATHOGENESIS-RELATED GENE 1 (PR1) and PR2. Lesion phenotypes were also reversed by growing plants in liquid media containing either low calcium (~0.1 mM) or high nitrogen concentrations (~24 mM), which are conditions known to suppress SA-dependent autoimmunity. Yeast-based fluorescent lipid uptake assays revealed that ALA10 and ALA11 display overlapping substrate specificities, including the transport of LysoPC signaling lipids. 👉Together, these results establish that the biochemical functions of ALA8–12 are at least partially overlapping, and that deficiencies in cluster-2 ALAs result in an SA-dependent autoimmunity phenotype that has not been observed for flippase mutants with deficiencies in other ALA clusters. Read more: https://bit.ly/3MJ6LnK

"R-DeeP/TripepSVM identifies the RNA-binding OB-fold-like protein PatR as regulator of heterocyst patterning" with Agrisera antibodies to RPL1. To article: https://lnkd.in/dtRPYkzE

#ASH24 REM-422 incorporates a poison exon into MYB pre-mRNA, thereby suppressing the production of MYB mRNA. The poison exon contains a premature termination codon (PTC), which triggers nonsense-mediated decay (NMD) of the mRNA. As a result, MYB protein expression is inhibited, leading to reduced expression of key MYB-regulated genes, including BCL2, MYC, and FLT3.

If mRNA targeted by REM-422 is not completely degraded and is instead translated with a premature termination codon (PTC), could it be recognized as a neoantigen by CD8+ T cells?

Parkinson's Discovery Suggests We May Already Have an FDA-Approved Treatment Pathologic α-synuclein (α-syn) spreads from cell-to-cell, in part, through binding to the lymphocyte-activation gene 3 (Lag3). Here we report that amyloid β precursor-like protein 1 (Aplp1) interacts with Lag3 that facilitates the binding, internalization, transmission, and toxicity of pathologic α-syn. Deletion of both Aplp1 and Lag3 eliminates the loss of dopaminergic neurons and the accompanying behavioral deficits induced by α-syn preformed fibrils (PFF). Anti-Lag3 prevents the internalization of α-syn PFF by disrupting the interaction of Aplp1 and Lag3, and blocks the neurodegeneration induced by α-syn PFF in vivo. The identification of Aplp1 and the interplay with Lag3 for α-syn PFF induced pathology deepens our insight about molecular mechanisms of cell-to-cell transmission of pathologic α-syn and provides additional targets for therapeutic strategies aimed at preventing neurodegeneration in Parkinson’s disease and related α-synucleinopathies. https://lnkd.in/eWWiTJpS

#ASH24 RGT-61159 and REM-422 manipulate the RNA splicing machinery to incorporate typically excluded poison or cryptic exons into MYB pre-mRNA. These exons contain premature termination codons (PTCs), which prevent the proper translation of mRNA. As a result, the cell detects these faulty mRNAs and degrades them via the nonsense-mediated decay (NMD) pathway. If these two drugs fail to degrade their target mRNA completely, allowing some translation to occur, the resulting protein fragments may act as neoantigens. Given that the generation of neoantigens relies on incomplete mRNA degradation by NMD, which approach is more likely to result in reduced degradation efficiency and thereby produce peptide fragments with higher immunogenicity?

Recombinant Bovine Basic Fibroblast Growth Factor（rbbFGF）  Basic fibroblast growth factor (also known as basic FGF, bFGF, FGF2, FGF- β or heparin-binding growth factor) is a pleiotropic cytokine and one of the prototypic members of the heparin-binding FGF family. In vivo, the basic fibroblast growth factor is produced by a variety of cells, including cardiomyocytes, fibroblasts, and vascular cells. Basic fibroblast growth factor regulates a variety of processes, including cell proliferation, differentiation, survival, adhesion, exercise, apoptosis, limb formation and wound healing. Basic FGF can be used to study angio-genesis, mitosis of fibroblasts, axonal growth, receptor binding and tyrosine phosphorylation of PC-12 cells. The angiogenic effects of FGF-basic can produce beneficial cardioprotection during acute heart injury. This product is recombinant bovine basic fibroblast growth factor(rbbFGF), which has the same biological activity as bovine basic fibroblast growth factor.  #cell #growthfactor #biotech #biological #biology #biopharmaceuticals #geneticengineering #bfgf https://lnkd.in/ehJakRCN

The transcriptional regulator Lrp activates the expression of genes involved in the biosynthesis of tilimycin and tilivalline enterotoxins in Klebsiella oxytoca The toxigenic Klebsiella oxytoca strains secrete tilymicin and tilivalline enterotoxins, which cause antibiotic-associated hemorrhagic colitis. Both enterotoxins are non-ribosomal peptides synthesized by enzymes encoded in two divergent operons clustered in a pathogenicity island. The transcriptional regulator Lrp (leucine-responsive regulatory protein) controls the expression of several bacterial genes involved in virulence. In this work, we have uncovered novel findings that have significant implications. We determined the transcriptional expression of aroX and npsA, the first genes of each tilimycin (TM)/tilivalline (TV) biosynthetic operon in K. oxytoca MIT 09-7231 wild-type and its derivatives Δlrp mutant and complemented strains. Our results suggest that Lrp directly activates the transcription of both aroX and npsA genes by binding to the intergenic regulatory region in a leucine-dependent manner. Furthermore, the lack of Lrp significantly diminished the cytotoxicity of K. oxytoca on HeLa cells due to reduced production of TM and TV. Altogether, our data present a new perspective on the role of Lrp as a regulator in cytotoxin-producing K. oxytoca strains and how it controls the expression of genes involved in the biosynthesis of their main virulence factors. https://lnkd.in/gjNg_iAs

L-tyrosine disodium salt can be used as a component of cell culture medium for routine cell culture and the biological production of recombinant proteins and monoclonal antibodies. L-tyrosine is a polar, naturally occurring non essential amino acid that is added to proteins according to the genetic code. It has phenolic functional groups, which make tyrosine residues in proteins the main receptors for reactions, such as phosphorylation/dephosphorylation, which is important for cell signaling. It is also a precursor to various neurotransmitters and hormones. L-tyrosine disodium salt is an improved L-tyrosine with better solubility