Publications by authors named "Karthigeyan Dhanasekaran"

The formation of clusters in non-aromatic molecules can give rise to unconventional luminescence or clusteroluminescence. Typically containing heteroatoms without extended conjugation or aromatic rings, these molecules have drawn much attention owing to the prospects of label-free biological imaging. However, their applications have been limited due to the lack of knowledge of the underlying mechanism.

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The reversible acetylation of specific Lysine residues of histones plays crucial role in the epigenetic regulation of chromatin activity. Importantly, perturbations of acetylation-deacetylation dynamics have important implications for cancer and neurological disorders. There are 18 human HDACs including sirtuins.

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The eukaryotic genome is enclosed in a nuclear envelope that protects it from potentially damaging cellular activities and physically segregates transcription and translation.Transport across the NE is highly regulated and occurs primarily the macromolecular nuclear pore complexes.Loss of nuclear compartmentalization due to defects in NPC function and NE integrity are tied to neurological and ageing disorders like Alzheimer's, viral pathogenesis, immune disorders, and cancer progression.

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Article Synopsis
  • Aurora kinases are special proteins that help cells divide and are linked to cancer development.
  • Researchers found that one specific aurora kinase, called AurkA, does more than helping cells divide; it also affects a protein named E2F4, which is important for muscle development.
  • When E2F4 didn't get properly modified by AurkA, it stayed in the cell's nucleus, preventing muscle growth and disrupting important genes needed for making muscles and energy.
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Aurora kinases are the most commonly targeted mitotic kinases in the intervention of cancer progression. Here, we report a resorcinol derivative, 5-methyl-4-(2-thiazolylazo) resorcinol (PTK66), a dual inhibitor of Aurora A and Aurora B kinases. PTK66 is a surface binding non-ATP analogue inhibitor that shows a mixed pattern of inhibition against both of Aurora A and B kinases.

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Positive coactivator 4 (PC4), a human transcriptional coactivator, is involved in diverse processes like chromatin organization and transcription regulation. It is hyperphosphorylated during mitosis, with unknown significance. For the first time, we demonstrate the function of PC4 outside the nucleus upon nuclear envelope breakdown.

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Article Synopsis
  • Scientists have found a cool way to use a technique called surface-enhanced Raman spectroscopy (SERS) to see how small molecules, like the drug felodipine, attach to important proteins.
  • They showed that felodipine specifically binds to a protein called Aurora A kinase and can help slow down cancer growth in mice.
  • This research helps to identify special spots on proteins, which could lead to new medicines that target similar proteins in the body.
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The functional association of NPM1 with Aurora kinases is well documented. Surprisingly, although NPM1 is a well characterized phosphoprotein, it is unknown whether it is a substrate of Aurora kinases. We have found that Aurora kinases A and B can phosphorylate NPM1 at a single serine residue, Ser125, in vitro and in vivo.

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Among the different posttranslational modifications (PTMs) that significantly regulate the protein function, lysine acetylation has become the major focus, especially to understand the epigenetic role of the acetyltransferases, in cellular physiology. Furthermore, dysfunction of these acetyltransferases is well documented under pathophysiological conditions. Therefore, it is important to understand the dynamic structure-function relationship of acetyltransferases in a relatively less complicated and faster method, which could be efficiently exploited to design and synthesis of small molecule modulators (activators/inhibitors) of these enzymes for in vivo functional analysis and therapeutic purposes.

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The Genome of a eukaryotic cell harbors genetic material in the form of DNA which carries the hereditary information encoded in their bases. Nucleotide bases of DNA are transcribed into complimentary RNA bases which are further translated into protein, performing defined set of functions. The central dogma of life ensures sequential flow of genetic information among these biopolymers.

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Histone modifications; acetylation, methylation (both Lysine and Arginine) etc., at different positions regulates the chromatin fluidity and function in a combinatorial manner, which could be referred as an epigenetic language. In the context of transcription, histone acetylation, methylation and phosphorylation at specific sites, especially at the N-terminal tails of histones play very important roles in activation and/or repression.

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The Aurora A kinase belongs to serine/threonine group of kinases, well known for its role in cell cycle, especially in the regulation of mitosis. Numerous substrates of Aurora A kinase have been identified, which are predominantly related to cell cycle progression while some of them are transcription factors. Aurora A-mediated phosphorylation can either directly or indirectly regulate the function of its substrates.

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