About: The PGRS Domain of Mycobacterium tuberculosis PE_PGRS Protein Rv0297 Is Involved in Endoplasmic Reticulum Stress-Mediated Apoptosis through Toll-Like Receptor 4

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About: The PGRS Domain of Mycobacterium tuberculosis PE_PGRS Protein Rv0297 Is Involved in Endoplasmic Reticulum Stress-Mediated Apoptosis through Toll-Like Receptor 4 Goto Sponge NotDistinct Permalink

An Entity of Type : schema:ScholarlyArticle, within Data Space : wasabi.inria.fr associated with source document(s)

Attributes	Values
type	Academic Article research paper schema:ScholarlyArticle
isDefinedBy	Covid-on-the-Web dataset
has title	The PGRS Domain of Mycobacterium tuberculosis PE_PGRS Protein Rv0297 Is Involved in Endoplasmic Reticulum Stress-Mediated Apoptosis through Toll-Like Receptor 4
Creator	Grover, Sonam Kohli, Sakshi Semmler, Torsten Sharma, Tarina Singh, Aditi Singh, Yadvir Tedin, Karsten Wieler, Lothar Ehtesham, Nasreen Hasnain, Seyed Bhaskar, Sangeeta
Source	PMC
abstract	The genome of Mycobacterium tuberculosis, the causal organism of tuberculosis (TB), encodes a unique protein family known as the PE/PPE/PGRS family, present exclusively in the genus Mycobacterium and nowhere else in the living kingdom, with largely unexplored functions. We describe the functional significance of the PGRS domain of Rv0297, a member of this family. In silico analyses revealed the presence of intrinsically disordered stretches and putative endoplasmic reticulum (ER) localization signals in the PGRS domain of Rv0297 (Rv0297PGRS). The PGRS domain aids in ER localization, which was shown by infecting macrophage cells with M. tuberculosis and by overexpressing the protein by transfection in macrophage cells followed by activation of the unfolded protein response, as evident from increased expression of GRP78/GRP94 and CHOP/ATF4, leading to disruption of intracellular Ca(2+) homeostasis and increased nitric oxide (NO) and reactive oxygen species (ROS) production. The consequent activation of the effector caspase-8 resulted in apoptosis of macrophages, which was Toll-like receptor 4 (TLR4) dependent. Administration of recombinant Rv0297PGRS (rRv0297PGRS) also exhibited similar effects. These results implicate a hitherto-unknown role of the PGRS domain of the PE_PGRS protein family in ER stress-mediated cell death through TLR4. Since this protein is already known to be present at later stages of infection in human granulomas it points to the possibility of it being employed by M. tuberculosis for its dissemination via an apoptotic mechanism.
has issue date	2018-06-19(xsd:dateTime)
bibo:doi	10.1128/mbio.01017-18
bibo:pmid	29921671
has license	cc-by
sha1sum (hex)	d921cd2d71ffa5577a0d2c534da20f6780b3a564
schema:url	https://doi.org/10.1128/mbio.01017-18
resource representing a document's title	The PGRS Domain of Mycobacterium tuberculosis PE_PGRS Protein Rv0297 Is Involved in Endoplasmic Reticulum Stress-Mediated Apoptosis through Toll-Like Receptor 4
has PubMed Central identifier	PMC6016250
has PubMed identifier	29921671
schema:publication	mBio
resource representing a document's body	covid:d921cd2d71ffa5577a0d2c534da20f6780b3a564#body_text
is schema:about of	named entity 'FAVOR' named entity 'HOST CELLS' named entity 'ENDOPLASMIC RETICULUM' named entity 'DEFENSE MECHANISM' named entity 'GRANULOMAS' named entity 'LATER' named entity 'AIDS' named entity 'INTRACELLULAR' named entity 'CASPASE-8' named entity 'MEDIATED' named entity 'PROTECTING' named entity 'TOLL-LIKE RECEPTOR 4' named entity 'GENERALLY' named entity 'SIGNIFICANCE' named entity 'HOMEOSTASIS' named entity 'GENOME OF MYCOBACTERIUM TUBERCULOSIS' named entity 'INCREASED' named entity 'DOMAIN' named entity 'UNIQUE' named entity 'M. TUBERCULOSIS' named entity 'SIGNALS' named entity 'INDUCE' named entity 'IN SILICO' named entity 'POINTS' named entity 'ER LOCALIZATION' named entity 'FAMILY' named entity 'DEPENDENT' named entity 'MACROPHAGES' named entity 'STAGES' named entity 'PRODUCTION' named entity 'MYCOBACTERIUM' named entity 'FUNCTIONS' named entity 'MICE' named entity 'KNOWN' named entity 'disease' named entity 'granulomas' named entity 'protein' named entity 'bacterium' named entity 'tuberculosis' named entity 'Mycobacterium tuberculosis' named entity 'localizing' named entity 'DOMAIN' named entity 'TOLL-LIKE RECEPTOR 4' named entity 'MYCOBACTERIUM TUBERCULOSIS' named entity 'GENUS' named entity 'DISSEMINATING' named entity 'APOPTOTIC' named entity 'EFFECTS' named entity 'DESCRIBE' named entity 'RECOMBINANT' named entity 'BACTERIUM' named entity 'INFECTION' named entity 'LOCALIZATION' named entity 'TRANSFECTION' named entity 'THESE' named entity 'ACTIVATION' named entity 'REVEALED' named entity 'DISORDERED' named entity 'INCREASED EXPRESSION' named entity 'DISEASE' named entity 'PE_PGRS5' named entity 'APOPTOSIS' named entity 'ORGANISM' named entity 'TLR4' named entity 'MACROPHAGE' named entity 'UNKNOWN ROLE' named entity 'HUMANS' named entity 'LOCALIZING' named entity 'STUDY' named entity 'WHERE' named entity 'UNFOLDED PROTEIN RESPONSE'

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