Imperial College London

Avinash R. Shenoy

Faculty of MedicineDepartment of Medicine

Non-Clinical Lecturer in Molecular Microbiology
 
 
 
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Contact

 

+44 (0)20 7594 3785a.shenoy Website

 
 
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Location

 

4.40AFlowers buildingSouth Kensington Campus

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Summary

 

Publications

Publication Type
Year
to

36 results found

Sanchez-Garrido J, Sancho-Shimizu V, Shenoy AR, 2018, Regulated proteolysis of p62/SQSTM1 enables differential control of autophagy and nutrient sensing., Sci Signal, Vol: 11

The multidomain scaffold protein p62 (also called sequestosome-1) is involved in autophagy, antimicrobial immunity, and oncogenesis. Mutations in SQSTM1, which encodes p62, are linked to hereditary inflammatory conditions such as Paget's disease of the bone, frontotemporal dementia (FTD), amyotrophic lateral sclerosis, and distal myopathy with rimmed vacuoles. Here, we report that p62 was proteolytically trimmed by the protease caspase-8 into a stable protein, which we called p62TRM We found that p62TRM, but not full-length p62, was involved in nutrient sensing and homeostasis through the mechanistic target of rapamycin complex 1 (mTORC1). The kinase RIPK1 and caspase-8 controlled p62TRM production and thus promoted mTORC1 signaling. An FTD-linked p62 D329G polymorphism and a rare D329H variant could not be proteolyzed by caspase-8, and these noncleavable variants failed to activate mTORC1, thereby revealing the detrimental effect of these mutations. These findings on the role of p62TRM provide new insights into SQSTM1-linked diseases and mTORC1 signaling.

JOURNAL ARTICLE

Ahmad L, Mashbat B, Leung C, Brookes C, Hamad S, Krokowski S, Shenoy AR, Lorenzo L, Levin M, O'Hare P, Zhang S-Y, Casanova J-L, Mostowy S, Sancho-Shimizu Vet al., 2018, Human TANK-binding kinase 1 is required for early autophagy induction upon herpes simplex virus 1 infection., J Allergy Clin Immunol

JOURNAL ARTICLE

Shenoy AR, Furniss RCD, Goddard PJ, Clements Aet al., 2018, Modulation of Host Cell Processes by T3SS Effectors, ESCHERICHIA COLI, A VERSATILE PATHOGEN, Editors: Frankel, Ron, Publisher: SPRINGER INTERNATIONAL PUBLISHING AG, Pages: 73-115, ISBN: 978-3-319-99663-9

BOOK CHAPTER

Bist P, Cheong WS, Ng A, Dikshit N, Kim B-H, Pulloor NK, Khameneh HJ, Hedl M, Shenoy AR, Balamuralidhar V, Malik NBA, Hong M, Neutzner A, Chin K-C, Kobayashi KS, Bertoletti A, Mortellaro A, Abraham C, MacMicking JD, Xavier RJ, Sukumaran Bet al., 2017, E3 Ubiquitin ligase ZNRF4 negatively regulates NOD2 signalling and induces tolerance to MDP, NATURE COMMUNICATIONS, Vol: 8, ISSN: 2041-1723

JOURNAL ARTICLE

Mazon-Moya MJ, Willis AR, Torraca V, Boucontet L, Shenoy AR, Colucci-Guyon E, Mostowy Set al., 2017, Septins restrict inflammation and protect zebrafish larvae from Shigella infection, PLOS PATHOGENS, Vol: 13, ISSN: 1553-7366

JOURNAL ARTICLE

Pallett MA, Crepin VF, Serafini N, Habibzay M, Kotik O, Sanchez-Garrido J, Di Santo JP, Shenoy AR, Berger CN, Frankel Get al., 2017, Bacterial virulence factor inhibits caspase-4/11 activation in intestinal epithelial cells, MUCOSAL IMMUNOLOGY, Vol: 10, Pages: 602-612, ISSN: 1933-0219

JOURNAL ARTICLE

Eldridge MJG, Sanchez-Garrido J, Hoben GF, Goddard PJ, Shenoy ARet al., 2017, The Atypical Ubiquitin E2 Conjugase UBE2L3 Is an Indirect Caspase-1 Target and Controls IL-1 beta Secretion by Inflammasomes, CELL REPORTS, Vol: 18, Pages: 1285-1297, ISSN: 2211-1247

JOURNAL ARTICLE

Thurston TLM, Matthews SA, Jennings E, Alix E, Shao F, Shenoy AR, Birrell MA, Holden DWet al., 2016, Growth inhibition of cytosolic Salmonella by caspase-1 and caspase-11 precedes host cell death, NATURE COMMUNICATIONS, Vol: 7, ISSN: 2041-1723

JOURNAL ARTICLE

Surana S, Shenoy AR, Krishnan Y, 2015, Designing DNA nanodevices for compatibility with the immune system of higher organisms, NATURE NANOTECHNOLOGY, Vol: 10, Pages: 741-747, ISSN: 1748-3387

JOURNAL ARTICLE

Mostowy S, Shenoy AR, 2015, The cytoskeleton in cell-autonomous immunity: structural determinants of host defence, NATURE REVIEWS IMMUNOLOGY, Vol: 15, Pages: 559-573, ISSN: 1474-1733

JOURNAL ARTICLE

Eldridge MJG, Shenoy AR, 2015, Antimicrobial inflammasomes: unified signalling against diverse bacterial pathogens, CURRENT OPINION IN MICROBIOLOGY, Vol: 23, Pages: 32-41, ISSN: 1369-5274

JOURNAL ARTICLE

Kim B-H, Shenoy AR, Kumar P, Bradfield CJ, MacMicking JDet al., 2012, IFN-Inducible GTPases in Host Cell Defense, CELL HOST & MICROBE, Vol: 12, Pages: 432-444, ISSN: 1931-3128

JOURNAL ARTICLE

Matsuzawa T, Kim B-H, Shenoy AR, Kamitani S, Miyake M, Macmicking JDet al., 2012, IFN-γ elicits macrophage autophagy via the p38 MAPK signaling pathway., J Immunol, Vol: 189, Pages: 813-818

Autophagy is a major innate immune defense pathway in both plants and animals. In mammals, this cascade can be elicited by cytokines (IFN-γ) or pattern recognition receptors (TLRs and nucleotide-binding oligomerization domain-like receptors). Many signaling components in TLR- and nucleotide-binding oligomerization domain-like receptor-induced autophagy are now known; however, those involved in activating autophagy via IFN-γ remain to be elucidated. In this study, we engineered macrophages encoding a tandem fluorescently tagged LC3b (tfLC3) autophagosome reporter along with stably integrated short hairpin RNAs to demonstrate IFN-γ-induced autophagy required JAK 1/2, PI3K, and p38 MAPK but not STAT1. Moreover, the autophagy-related guanosine triphosphatase Irgm1 proved dispensable in both stable tfLC3-expressing RAW 264.7 and tfLC3-transduced Irgm1(-/-) primary macrophages, revealing a novel p38 MAPK-dependent, STAT1-independent autophagy pathway that bypasses Irgm1. These unexpected findings have implications for understanding how IFN-γ-induced autophagy is mobilized within macrophages for inflammation and host defense.

JOURNAL ARTICLE

Shenoy AR, Wellington DA, Kumar P, Kassa H, Booth CJ, Cresswell P, MacMicking JDet al., 2012, GBP5 Promotes NLRP3 Inflammasome Assembly and Immunity in Mammals, SCIENCE, Vol: 336, Pages: 481-485, ISSN: 0036-8075

JOURNAL ARTICLE

Kim B-H, Shenoy AR, Kumar P, Das R, Tiwari S, MacMicking JDet al., 2011, A family of IFN-γ-inducible 65-kD GTPases protects against bacterial infection., Science, Vol: 332, Pages: 717-721

Immune interferon gamma (IFN-γ) is essential for mammalian host defense against intracellular pathogens. IFN-γ induces nearly 2000 host genes, yet few have any assigned function. Here, we examined a complete mouse 65-kilodalton (kD) guanylate-binding protein (Gbp) gene family as part of a 43-member IFN-γ-inducible guanosine triphosphatase (GTPase) superfamily in mouse and human genomes. Family-wide loss-of-function analysis found that at least four Gbps--Gbp1, Gbp6, Gbp7, and Gbp10--conferred cell-autonomous immunity to listerial or mycobacterial infection within macrophages and gene-deficient animals. These Gbps solicited host defense proteins, including the phagocyte oxidase, antimicrobial peptides, and autophagy effectors, to kill intracellular bacteria. Thus, specific 65-kD Gbps coordinate a potent oxidative and vesicular trafficking program to protect the host from infection.

JOURNAL ARTICLE

Biswas KH, Shenoy AR, Dutta A, Visweswariah SSet al., 2009, The Evolution of Guanylyl Cyclases as Multidomain Proteins: Conserved Features of Kinase-Cyclase Domain Fusions, JOURNAL OF MOLECULAR EVOLUTION, Vol: 68, Pages: 587-602, ISSN: 0022-2844

JOURNAL ARTICLE

Tyagi R, Shenoy AR, Visweswariah SS, 2009, Characterization of an Evolutionarily Conserved Metallophosphoesterase That Is Expressed in the Fetal Brain and Associated with the WAGR Syndrome, JOURNAL OF BIOLOGICAL CHEMISTRY, Vol: 284, Pages: 5217-5228, ISSN: 0021-9258

JOURNAL ARTICLE

Dass BKM, Sharma R, Shenoy AR, Mattoo R, Visweswariah SSet al., 2008, Cyclic AMP in mycobacteria: Characterization and functional role of the rv1647 ortholog in Mycobacterium smegmatis, JOURNAL OF BACTERIOLOGY, Vol: 190, Pages: 3824-3834, ISSN: 0021-9193

JOURNAL ARTICLE

Shenoy AR, Capuder M, Draskovic P, Lamba D, Visweswariah SS, Podobnik Met al., 2007, Structural and biochemical analysis of the Rv0805 cyclic nucleotide phosphodiesterase from Mycobacterium tuberculosis, JOURNAL OF MOLECULAR BIOLOGY, Vol: 365, Pages: 211-225, ISSN: 0022-2836

JOURNAL ARTICLE

Shenoy AR, Kim B-H, Choi H-P, Matsuzawa T, Tiwari S, MacMicking JDet al., 2007, Emerging themes in IFN-gamma-induced macrophage immunity by the p47 and p65 GTPase families, IMMUNOBIOLOGY, Vol: 212, Pages: 771-784, ISSN: 0171-2985

JOURNAL ARTICLE

Shenoy AR, Visweswariah SS, 2006, New messages from old messengers: cAMP and mycobacteria, TRENDS IN MICROBIOLOGY, Vol: 14, Pages: 543-550, ISSN: 0966-842X

JOURNAL ARTICLE

Macario AJL, Brocchieri L, Shenoy AR, de Macario ECet al., 2006, Evolution of a protein-folding machine: Genomic and evolutionary analyses reveal three lineages of the archaeal hsp70(dnaK) gene, JOURNAL OF MOLECULAR EVOLUTION, Vol: 63, Pages: 74-86, ISSN: 0022-2844

JOURNAL ARTICLE

Shenoy AR, Visweswariah SS, 2006, Mycobacterial adenylyl cyclases: Biochemical diversity and structural plasticity, FEBS LETTERS, Vol: 580, Pages: 3344-3352, ISSN: 0014-5793

JOURNAL ARTICLE

Ketkar AD, Shenoy AR, Ramagopal UA, Visweswariah SS, Suguna Ket al., 2006, A structural basis for the role of nucleotide specifying residues in regulating the oligomerization of the Rv1625c adenylyl cyclase from M. tuberculosis., J Mol Biol, Vol: 356, Pages: 904-916, ISSN: 0022-2836

The Rv1625c Class III adenylyl cyclase from Mycobacterium tuberculosis is a homodimeric enzyme with two catalytic centers at the dimer interface, and shows sequence similarity with the mammalian adenylyl and guanylyl cyclases. Mutation of the substrate-specifying residues in the catalytic domain of Rv1625c, either independently or together, to those present in guanylyl cyclases not only failed to confer guanylyl cyclase activity to the protein, but also severely abrogated the adenylyl cyclase activity of the enzyme. Biochemical analysis revealed alterations in the behavior of the mutants on ion-exchange chromatography, indicating differences in the surface-exposed charge upon mutation of substrate-specifying residues. The mutant proteins showed alterations in oligomeric status as compared to the wild-type enzyme, and differing abilities to heterodimerize with the wild-type protein. The crystal structure of a mutant has been solved to a resolution of 2.7A. On the basis of the structure, and additional biochemical studies, we provide possible reasons for the altered properties of the mutant proteins, as well as highlight unique structural features of the Rv1625c adenylyl cyclase.

JOURNAL ARTICLE

Jaleel M, Saha S, Shenoy AR, Visweswariah SSet al., 2006, The kinase homology domain of receptor guanylyl cyclase C: ATP binding and identification of an adenine nucleotide sensitive site, BIOCHEMISTRY, Vol: 45, Pages: 1888-1898, ISSN: 0006-2960

JOURNAL ARTICLE

Shenoy AR, Sreenath N, Podobnik M, Kovacevic M, Visweswariah SSet al., 2005, The Rv0805 gene from Mycobacterium tuberculosis encodes a 3 ',5 '-cyclic nucleotide phosphodiesterase: Biochemical and mutational analysis, BIOCHEMISTRY, Vol: 44, Pages: 15695-15704, ISSN: 0006-2960

JOURNAL ARTICLE

Shenoy AR, Srinivas A, Mahalingam M, Visweswariah SSet al., 2005, An adenylyl cyclase pseudogene in Mycobacterium tuberculosis has a functional ortholog in Mycobacterium avium, BIOCHIMIE, Vol: 87, Pages: 557-563, ISSN: 0300-9084

JOURNAL ARTICLE

Shenoy AR, Sreenath NP, Mahalingam M, Visweswariah SSet al., 2005, Characterization of phylogenetically distant members of the adenylate cyclase family from mycobacteria: Rv1647 from Mycobacterium tuberculosis and its orthologue ML1399 from M. leprae, BIOCHEMICAL JOURNAL, Vol: 387, Pages: 541-551, ISSN: 0264-6021

JOURNAL ARTICLE

Jaleel M, Shenoy AR, Visweswariah SS, 2004, Tyrphostins are inhibitors of guanylyl and adenylyl cyclases, BIOCHEMISTRY, Vol: 43, Pages: 8247-8255, ISSN: 0006-2960

JOURNAL ARTICLE

Shenoy AR, Visweswariah SS, 2004, Class III nucleotide cyclases in bacteria and archaebacteria: lineage-specific expansion of adenylyl cyclases and a dearth of guanylyl cyclases, FEBS LETTERS, Vol: 561, Pages: 11-21, ISSN: 0014-5793

JOURNAL ARTICLE

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