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Sanjeev Shukla
Indian Institute of Science Education and Research, Bhopal
CancerAlternative splicingExonRNA splicingBiology
17Publications
8H-index
857Citations
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Publications 17
Newest
#1Srinivasa Rao Adusumalli (Indian Institute of Science Education and Research, Bhopal)H-Index: 4
#2Dattatraya Gautam Rawale (Indian Institute of Science Education and Research, Bhopal)H-Index: 3
Last. Vishal Rai (Indian Institute of Science Education and Research, Bhopal)H-Index: 11
view all 8 authors...
The necessity for precision labeling of proteins emerged during the efforts to understand and regulate their structure and function. It demands selective attachment of tags such as affinity probes, fluorophores, and potent cytotoxins. Here, we report a method that enables single-site labeling of a high-frequency Lys residue in the native proteins. At first, the enabling reagent forms stabilized imines chemoselectively with multiple solvent-accessible Lys residues. These linchpins create the oppo...
2 CitationsSource
#1Deepak Pant (Indian Institute of Science Education and Research, Bhopal)H-Index: 1
Last. Sanjeev ShuklaH-Index: 8
view all 4 authors...
The tumor microenvironment is marked by gradients in the level of oxygen and nutrients, with oxygen levels reaching a minimum at the core of the tumor, a condition known as tumor hypoxia. Mediated by members of the HIF family of transcription factors, hypoxia leads to a more aggressive tumor phenotype by transactivation of several genes as well as reprogramming of pre-mRNA splicing. Intragenic DNA methylation, which is known to affect alternative splicing in cancer, could be one of several reaso...
1 CitationsSource
#1Sandhya Yadav (Indian Institute of Science Education and Research, Bhopal)H-Index: 2
#2Somnath D. Bhagat (Indian Institute of Science Education and Research, Bhopal)H-Index: 3
Last. Sanjeev Shukla (Indian Institute of Science Education and Research, Bhopal)H-Index: 8
view all 6 authors...
The deregulated alternative splicing of key glycolytic enzyme, Pyruvate Kinase muscle isoenzyme (PKM) is implicated in metabolic adaptation of cancer cells. The splicing switch from normal PKM1 to cancer-specific PKM2 isoform allows the cancer cells to meet their energy and biosynthetic demands, thereby facilitating the cancer cells growth. We have investigated the largely unexplored epigenetic mechanism of PKM splicing switch in head and neck cancer (HNC) cells. Considering the reversible natur...
2 CitationsSource
Chemical biology research often requires precise covalent attachment of labels to the native proteins. Such methods are sought after to probe, design, and regulate the properties of proteins. At present, this demand is largely unmet due to the lack of empowering chemical technology. Here, we report a chemical platform that enables site-selective labeling of native proteins. Initially, a reversible intermolecular reaction places the “chemical linchpins” globally on all the accessible Lys residues...
14 CitationsSource
#1Amit Gupta (Indian Institute of Science Education and Research, Bhopal)H-Index: 3
#2Athira Ajith (Indian Institute of Technology Madras)H-Index: 1
Last. Sanjeev Shukla (Indian Institute of Science Education and Research, Bhopal)H-Index: 8
view all 6 authors...
The histone modifiers (HMs) are crucial for chromatin dynamics and gene expression; however, their dysregulated expression has been observed in various abnormalities including cancer. In this study, we have analyzed the expression of HMs in microarray profiles of head and neck cancer (HNC), wherein a highly significant overexpression of p21-activated kinase 2 (PAK2) was identified which was further validated in HNC patients. The elevated expression of PAK2 positively correlated with enhanced cel...
4 CitationsSource
#1Maheshwerreddy Chilamari (Indian Institute of Science Education and Research, Bhopal)H-Index: 3
#2Neetu Kalra (Indian Institute of Science Education and Research, Bhopal)H-Index: 2
Last. Vishal Rai (Indian Institute of Science Education and Research, Bhopal)H-Index: 11
view all 4 authors...
We report a chemoselective and site-selective approach that distinguishes one Lys from its multiple copies, N-terminus, and other competitors. The phospha-Mannich protocol works with multiple proteins and installs probes without structural and functional perturbations. It delivers an antibody–drug conjugate with selective anti-proliferative activity towards HER2 expressing SKBR3 breast cancer cells.
4 CitationsSource
#1Smriti Singh (Indian Institute of Science Education and Research, Bhopal)H-Index: 4
#2Sathiya Pandi Narayanan (Indian Institute of Science Education and Research, Bhopal)H-Index: 3
Last. Sanjeev Shukla (Indian Institute of Science Education and Research, Bhopal)H-Index: 8
view all 10 authors...
Abstract Aberrant alternative splicing and epigenetic changes are both associated with various cancers, but epigenetic regulation of alternative splicing in cancer is largely unknown. Here we report that the intragenic DNA methylation-mediated binding of Brother of Regulator of Imprinted Sites (BORIS) at the alternative exon of Pyruvate Kinase (PKM) is associated with cancer-specific splicing that promotes the Warburg effect and breast cancer progression. Interestingly, the inhibition of DNA met...
9 CitationsSource
#1Sathiya Pandi Narayanan (Indian Institute of Science Education and Research, Bhopal)H-Index: 3
#2Smriti Singh (Indian Institute of Science Education and Research, Bhopal)H-Index: 4
Last. Sanjeev Shukla (Indian Institute of Science Education and Research, Bhopal)H-Index: 8
view all 3 authors...
The discovery of an increasing number of alternative splicing events in the human genome highlighted that ∼94% of genes generate alternatively spliced transcripts that may produce different protein isoforms with diverse functions. It is now well known that several diseases are a direct and indirect consequence of aberrant splicing events in humans. In addition to the conventional mode of alternative splicing regulation by ‘ cis ’ RNA-binding sites and ‘ trans’ RNA-binding proteins, recent litera...
6 CitationsSource
#1Ryan J Marina (NIH: National Institutes of Health)H-Index: 1
#2David Sturgill (NIH: National Institutes of Health)H-Index: 22
Last. Shalini Oberdoerffer (NIH: National Institutes of Health)H-Index: 7
view all 10 authors...
Abstract Intragenic 5‐methylcytosine and CTCF mediate opposing effects on pre‐mRNA splicing: CTCF promotes inclusion of weak upstream exons through RNA polymerase II pausing, whereas 5‐methylcytosine evicts CTCF, leading to exon exclusion. However, the mechanisms governing dynamic DNA methylation at CTCF‐binding sites were unclear. Here, we reveal the methylcytosine dioxygenases TET1 and TET2 as active regulators of CTCF‐mediated alternative splicing through conversion of 5‐methylcytosine to its...
38 CitationsSource
#1Sathiya Pandi Narayanan (Indian Institute of Science Education and Research, Bhopal)H-Index: 3
#2Smriti Singh (Indian Institute of Science Education and Research, Bhopal)H-Index: 4
Last. Sanjeev Shukla (Indian Institute of Science Education and Research, Bhopal)H-Index: 8
view all 6 authors...
Abstract The histone demethylase KDM1A specifically demethylates lysine residues and its deregulation has been implicated in the initiation and progression of various cancers. However, KDM1A's molecular role and its pathological consequences, and prognostic significance in oral cancer remain less understood. In the present study, we sought to investigate the expression of KDM1A and its downstream role in oral cancer pathogenesis. By comparing mRNA expression profiles, we identified an elevated K...
7 CitationsSource
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