PXD017117

PXD017117 is an original dataset announced via ProteomeXchange.

Title	Infection-driven activation of transglutaminase 2 boosts glucose uptake and hexosamine biosynthesis
Description	Transglutaminase 2 (TG2) is a ubiquitous enzyme with transamidating activity. We report here that the expression and activity of TG2 are enhanced in cells infected with the obligate intracellular bacteria Chlamydia trachomatis. Genetic or pharmacological inhibition of TG2 activity impair bacterial development. We show that TG2 increases glucose import by up-regulating the transcription of the glucose transporter genes GLUT-1 and GLUT-3. Furthermore, TG2 activation drives one specific glucose-dependent pathway in the host, i.e. hexosamine biosynthesis. Mechanistically, we identify the glucosamine:fructose-6-phosphate amidotransferase (GFPT) among the substrates of TG2. GFPT modification by TG2 increases its enzymatic activity, resulting in higher levels of UDP-N-acetylglucosamine biosynthesis. As a consequence, TG2 activation results in increased protein O-GlcNAcylation. The correlation between TG2 transamidating activity and O-GlcNAcylation is disrupted in infected cells because host hexosamine biosynthesis is being exploited by the bacteria, in particular to assist their division. In conclusion, our work establishes TG2 as a key player in controlling glucose-derived metabolic pathways in mammalian cells, themselves hijacked by C. trachomatis to sustain their own metabolic needs.
HostingRepository	PRIDE
AnnounceDate	2020-02-27
AnnouncementXML	Submission_2020-05-20_04:40:07.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Magalie Duchateau
SpeciesList	scientific name: Chlamydia trachomatis E/C599; NCBI TaxID: 1100832; scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	L-methionine sulfoxide; NHS-LC-Biotin; N-acetylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive Plus

Revision	Datetime	Status	ChangeLog Entry
0	2020-01-15 02:46:04	ID requested
1	2020-02-27 01:44:13	announced
⏵ 2	2020-05-20 04:40:08	announced	2020-05-20: Updated publication reference for PubMed record(s): 32134139.

Maffei B, Laverri, è, re M, Wu Y, Triboulet S, Perrinet S, Duchateau M, Matondo M, Hollis RL, Gourley C, Rupp J, Keillor JW, Subtil A, Infection-driven activation of transglutaminase 2 boosts glucose uptake and hexosamine biosynthesis in epithelial cells. EMBO J, 39(8):e102166(2020) [pubmed]

submitter keyword: Chlamydia, GFPT, Hexosamine biosynthesis, O-GlcNAcylation, Transglutaminase 2

Agathe Subtil
contact affiliation	Agathe Subtil UMR3691 CNRS Cellular Biology of Microbial Infection Institut Pasteur 25, rue du Dr Roux 75015 Paris, France
contact email	agathe.subtil@pasteur.fr
lab head
Magalie Duchateau
contact affiliation	Institut Pasteur
contact email	magalie.duchateau@pasteur.fr
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD017117
     1. Label: PRIDE project
     2. Name: Infection-driven activation of transglutaminase 2 boosts glucose uptake and hexosamine biosynthesis