Proteomics

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Large scale profiling of the physiological impact of a potent anti-cancer agent inhibiting early protein maturation

ABSTRACT: Fumagillin and its derivatives are therapeutically-useful compounds for their capacity to reduce cancer progression. Fumagillin exerts a specific proliferation inhibition on endothelial cell lines and on several tumor lines. The specific molecular target of fumagillin is MetAP2, one of the two cytosolic MetAPs. MetAPs are in charge of N-terminal Methionine Excision, an essential pathway of cotranslational protein maturation. Why the inhibition of MetAP2 causes cell growth arrest in a subset class of cells is yet unknown. Here, we focus on a global large scale characterization of the N-terminal Methionine Excision pathway and the inhibition of one of its enzymes by fumagillin in a number of lines including cancer cell lines. N-termini profiling of responsive and unresponsive cells to fumagillin treatment was conducted using large scale proteomics approach

INSTRUMENT(S): LTQ Orbitrap Velos

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Endothelial Cell Of Umbilical Vein, Epithelial Cell, Obsolete Lymphoblast

SUBMITTER: Willy Bienvenut  

LAB HEAD: Willy V Bienvenut

PROVIDER: PXD002690 | Pride | 2017-01-02

REPOSITORIES: Pride

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Dataset's files

Source:
Action DRS
20130822_WIB_U87-Ctrl-Centricon_frac_3-6_CID_Ch1.dat Other
20130822_WIB_U87-Ctrl-Centricon_frac_3-6_CID_Ch1.raw Raw
20130822_WIB_U87-Ctrl-Centricon_frac_3-6_CID_Ch2.dat Other
20130822_WIB_U87-Ctrl-Centricon_frac_3-6_CID_Ch2.raw Raw
20130822_WIB_U87-ctrl-Centricon_frac_10-12_CID_Ch1.dat Other
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Publications

MetAP1 and MetAP2 drive cell selectivity for a potent anti-cancer agent in synergy, by controlling glutathione redox state.

Frottin Frédéric F   Bienvenut Willy V WV   Bignon Jérôme J   Jacquet Eric E   Vaca Jacome Alvaro Sebastian AS   Van Dorsselaer Alain A   Cianferani Sarah S   Carapito Christine C   Meinnel Thierry T   Giglione Carmela C  

Oncotarget 20160901 39

Fumagillin and its derivatives are therapeutically useful because they can decrease cancer progression. The specific molecular target of fumagillin is methionine aminopeptidase 2 (MetAP2), one of the two MetAPs present in the cytosol. MetAPs catalyze N-terminal methionine excision (NME), an essential pathway of cotranslational protein maturation. To date, it remains unclear the respective contribution of MetAP1 and MetAP2 to the NME process in vivo and why MetAP2 inhibition causes cell cycle arr  ...[more]

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