Dataset Information

SERUM_Protein expression profiling of serum and lungs at different stages of metastatic development in a human triple negative breast cancer xenograft model - Part 2

ABSTRACT: The main objective of this study was to evaluate the protein expression profiling of serum and lungs at different stages of metastatic development in a human triple negative MDA-MB

INSTRUMENT(S): Q Exactive

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Blood Serum

DISEASE(S): Breast Cancer

SUBMITTER: Frode Selheim

LAB HEAD: Linda Stuhr

PROVIDER: PXD010249 | Pride | 2019-05-07

REPOSITORIES: Pride

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Publications

Protein expression profiling of plasma and lungs at different stages of metastatic development in a human triple negative breast cancer xenograft model.

Tveitarås Maria K MK Selheim Frode F Sortland Kristina K Reed Rolf K RK Stuhr Linda L

PloS one 20190501 5

The main objective of this study was to identify single proteins or protein networks that might be used as diagnostic biomarkers or for therapeutic purposes by evaluating the protein expression profiling of plasma and lungs at different stages of metastatic development in a human triple negative MDA-MB-231 breast cancer xenograft model. MDA-MB-231 tumour cells were injected into the mammary fat pads on one side of the groin area. The mice were sacrificed day 19 (pre-metastases) and day 54 (metas ...[more]

PMID: 31042781

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Project description:Pathogenic microorganisms often secrete proteins or nucleic acids that mimic the structure and/or function of molecules expressed within their host counterparts. This molecular mimicry empowers pathogens to target and subvert critical host processes and helps establish their infectious paradigm. We report here that the intracellular bacterium Legionella pneumophila (L.p.) secretes a toxin named SidI (substrate of icm/dot transporter I) which possesses a transfer RNA (tRNA) like fold and functions as a mannosyl transferase enzyme. The 3.1 Å cryo-EM structure of SidI reveals an N-terminal domain that exhibits a characteristic ‘inverted L-shape’ and charge conservation that is present in two known protein mimics of tRNAs, the bacterial elongation factor EF-G and the mammalian release factor eRF1. In addition, SidI’s C-terminal domain adopts a glycosyl transferase B fold and shares considerable homology to a known mannosyl transferase. This molecular coupling of fold and enzymatic function allows SidI to bind to and enzymatically modify components of the host translational apparatus, including the ribosome, resulting in a robust block of protein synthesis that is comparable to the potency exhibited by the toxin ricin. Additionally, we uncovered that the translational pausing activated by SidI elicits a stress response signature that is highly similar to one activated by elongation inhibitors that target the ribosome and induce ribosome collisions. SidI-mediated perturbations to the ribosome activate the stress kinases ZAKα and p38, that in turn drive the accumulation of the protein activating transcription factor 3 (ATF3). Intriguingly, ATF3 escapes the translation block imposed by SidI, translocates to the nucleus, and subsequently orchestrates the transcription of stress-inducible genes that culminates in the activation of a cell death program. Thus, using Legionella and its effectors as tools, we have unravelled the role of a ribosome to nuclear signaling pathway that regulates cell fate.

Dataset Information

SERUM_Protein expression profiling of serum and lungs at different stages of metastatic development in a human triple negative breast cancer xenograft model - Part 2

Publications

Protein expression profiling of plasma and lungs at different stages of metastatic development in a human triple negative breast cancer xenograft model.

Similar Datasets

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