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P38a regulated networks in cancer cell homeostasis

ABSTRACT: p38a (encoded by MAPK14) is a protein kinase that regulates cellular responses to almost all types of environmental and intracellular stresses. Upon activation, p38a phosphorylates various substrates both in the cytoplasm and nucleus, allowing this pathway to regulate a wide variety of cellular processes, including cell proliferation, differentiation or survival. To investigate the signaling networks regulated by p38a during cancer cell homeostasis, we performed proteomic and phosphoproteomic analysis. Our study identified with high confidence 35 proteins and 114 phosphosites that are modulated by p38a, and highlighted the implication of other protein kinases, such as MK2 and mTOR, in p38a-regulated cellular processes. Moreover, functional analysis of the proteome and phosphoproteome data revealed an important contribution of p38a to the regulation of the processes of cell adhesion, DNA replication and RNA metabolism. We provide experimental evidence supporting that p38a negatively regulates cell-cell adhesion, and showed that this p38a function is likely mediated by the transcriptional modulation of the adaptor protein ArgBP2. Collectively, our results illustrate the complexity of the p38a regulated signaling networks, provide valuable information on p38a-dependent phosphorylation events in cancer cell homeostasis, and document a mechanism by which p38a regulates the adhesion capacity of cancer cells.

INSTRUMENT(S): Orbitrap Fusion Lumos

ORGANISM(S): Mus Musculus (mouse)

SUBMITTER: Marina Gay

LAB HEAD: Angel R. Nebreda

PROVIDER: PXD034051 | Pride | 2023-02-10

REPOSITORIES: Pride

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			Action	DRS
	2512_JJB_NoPh_RB1.raw	Raw
	2512_JJB_NoPh_RB2.raw	Raw
	2512_JJB_NoPh_RB2_2.raw	Raw
	2512_JJB_NoPh_RB3.raw	Raw
	2512_JJB_NoPh_RB3_2.raw	Raw

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