PXD009897

PXD009897 is an original dataset announced via ProteomeXchange.

Title	IKK Promotes Cytokine-Induced and Cancer-Associated AMPK Activity and Attenuates Phenformin-Induced Cell Death in LKB1-Deficient Cells
Description	The 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.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_04:12:27.845.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Ricardo Antonia
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	phosphorylated residue; iodoacetamide derivatized residue
Instrument	LTQ Orbitrap Velos

Revision	Datetime	Status	ChangeLog Entry
0	2018-05-25 01:43:39	ID requested
1	2018-07-16 05:37:38	announced
⏵ 2	2024-10-22 04:12:28	announced	2024-10-22: Updated project metadata.

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;

curator keyword: Biomedical

submitter keyword: IKK;AMPK

Inflammation

IL-1

Phenformin

Albert Baldwin
contact affiliation	Lineberger Comprehensive Cancer Center UNC Chapel Hill
contact email	albert_baldwin@med.unc.edu
lab head
Ricardo Antonia
contact affiliation	Mr.
contact email	rantonia@email.unc.edu
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2018/07/PXD009897

PRIDE project URI

• PRIDE
  1. PXD009897
     1. Label: PRIDE project
     2. Name: IKK Promotes Cytokine-Induced and Cancer-Associated AMPK Activity and Attenuates Phenformin-Induced Cell Death in LKB1-Deficient Cells