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PXD009897

PXD009897 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleIKK Promotes Cytokine-Induced and Cancer-Associated AMPK Activity and Attenuates Phenformin-Induced Cell Death in LKB1-Deficient Cells
DescriptionThe 5' AMP-activated protein kinase (AMPK) is a master energy sensing kinase that is regulated by phosphorylation of Thr172 in its activation loop. Three kinases can phosphorylate AMPK at Thr172: the tumor suppressor LKB1, CAMKK2 and TAK1. While LKB1- and CAMKK2-mediated AMPK Thr172 phosphorylation have been well-characterized, much less is known about TAK1-dependent AMPK phosphorylation. An important target of TAK1 is IκB kinase (IKK) which controls NF-B transcription factor activation. Here, we tested the hypothesis that IKK acted downstream of TAK1 to activate AMPK by phosphorylating Thr172. IKK was required for phosphorylation of Thr172 in AMPK in response to treatment with IL-1 or TNF- treatment or by TAK1 overexpression. Additionally, IKK regulated basal AMPK Thr172 phosphorylation in several cancer cell types independently of TAK1, indicating that other modes of IKK activation could lead to AMPK activation. We found that IKK directly phosphorylated AMPK at Thr172 independently of LKB1 or energy stress. This finding indicated that while LKB1 activates AMPK as a sensor of energetic stress, IKK activated AMPK in response to extracellular inflammatory signals and through distinct pathways downstream of IKK activation. Accordingly, in LKB1-deficient cells, IKK inhibition caused a reduction in AMPK Thr172 phosphorylation in response to the mitochondrial inhibitor phenformin. This response led to enhanced apoptosis and suggests that IKK inhibition in combination with phenformin could be used clinically to treat patients with LKB1-deficient cancers.
HostingRepositoryPRIDE
AnnounceDate2024-10-22
AnnouncementXMLSubmission_2024-10-22_04:12:27.845.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterRicardo Antonia
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationListphosphorylated residue; iodoacetamide derivatized residue
InstrumentLTQ Orbitrap Velos
Dataset History
RevisionDatetimeStatusChangeLog Entry
02018-05-25 01:43:39ID requested
12018-07-16 05:37:38announced
22024-10-22 04:12:28announced2024-10-22: Updated project metadata.
Publication List
Antonia RJ, Baldwin AS, IKK promotes cytokine-induced and cancer-associated AMPK activity and attenuates phenformin-induced cell death in LKB1-deficient cells. Sci Signal, 11(538):(2018) [pubmed]
10.1126/scisignal.aan5850;
Keyword List
curator keyword: Biomedical
submitter keyword: IKK;AMPK
Inflammation
IL-1
Phenformin
Contact List
Albert Baldwin
contact affiliationLineberger Comprehensive Cancer Center UNC Chapel Hill
contact emailalbert_baldwin@med.unc.edu
lab head
Ricardo Antonia
contact affiliationMr.
contact emailrantonia@email.unc.edu
dataset submitter
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Dataset FTP location
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PRIDE project URI
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