Proteomics

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Targeting PCNA in a subgroup of Multiple Myeloma cells inhibits the glycolysis and pentose phosphate pathway


ABSTRACT: PCNA is an essential protein in all cells with multiple well-known function in DNA replication and DNA repair. Recently, PCNA was shown to be involved in regulation of cellular signalling and central carbon metabolism via stabilizing the metabolic enzymes ENO1 and 6PGD. Furthermore, ATX-101, a PCNA targeting peptide currently in Phase II, was shown to reduce metabolite pools in the glycolysis and the pentose phosphate pathway (PPP) in multiple haematological cells. Here integrated analysis of signalome and metabolome data from multiple myeloma (MM) cells reveals large effects of ATX-101 on signalling, metabolism and red-ox regulation. The sensitivity to ATX-101 varied between the eight MM cell lines studied and a metabolic shift was detected in the sensitive cell lines. These cell lines were characterized by low endogenous levels of the redox metabolites NAD+, NADH and GSH. Interestingly, 11 proteins were pulled down from untreated cells from the sensitive cell lines while not from 9 other cancer cell lines or primary monocytes from three donors. These proteins could be potential biomarkers for MM cells with low red-ox capacity and hypersensitivity for inhibitors of glycolysis or the PPP.

INSTRUMENT(S): Q Exactive HF

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Blood Cell

SUBMITTER: Animesh Sharma  

LAB HEAD: Marit Otterlei

PROVIDER: PXD033510 | Pride | 2024-11-25

REPOSITORIES: Pride

Dataset's files

Source:
Action DRS
200313_SIRI_TK12_APIM4.raw Raw
200313_SIRI_TK12_APIM5.raw Raw
200313_SIRI_TK12_APIM6.raw Raw
200313_SIRI_TK12_CTR1.raw Raw
200313_SIRI_TK12_CTR1_20200323190746.raw Raw
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