Systematic analysis of BCR-ABL interactome in chronic myeloid leukemia

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216224%3A14740%2F17%3A00095713" target="_blank" >RIV/00216224:14740/17:00095713 - isvavai.cz</a>

Výsledek na webu

<a href="https://2017.febscongress.org/abstract_preview.aspx?idAbstractEnc=4424170093097092096093424170" target="_blank" >https://2017.febscongress.org/abstract_preview.aspx?idAbstractEnc=4424170093097092096093424170</a>

DOI - Digital Object Identifier

—

Jazyk výsledku

angličtina

Název v původním jazyce

Systematic analysis of BCR-ABL interactome in chronic myeloid leukemia

Popis výsledku v původním jazyce

Chronic myeloid leukemia (CML) is a myeloproliferative cancer that is caused by “Philadelphia chromosome” translocation that results in a formation of fusion protein BCR-ABL. This constitutively active tyrosine kinase is necessary and sufficient to cause CML. Several small molecule tyrosine kinase inhibitors (TKI) targeting BCR-ABL kinase activity had been developed and greatly improved CML prognosis. However, significant number of patients develops resistance to TKIs and relapse. Growing evidence shows the importance of other BCR-ABL interaction partners in CML pathogenesis. Precise elucidation of the interactome can lead to design of conceptually new drug targeting different pathways and overcoming TKI resistance. One of our goals is to elucidate precise binding interface among BCR-ABL and it’s “core complex” interaction partners. Our approach involves use of peptide microarrays, which allow us to map the binding interface with single amino acid resolution. Binding motifs discovered in unstructured parts of BCR-ABL can be used to generate synthetic peptide abolishing particular protein interaction. Furthermore, we created large pallet of BCR-ABL deletion/substitution mutants in order to verify interaction boundaries and co-immunoprecipitation experiments have yielded potential new binding sites for some of the core complex interactors.

Název v anglickém jazyce

Systematic analysis of BCR-ABL interactome in chronic myeloid leukemia

Popis výsledku anglicky

Chronic myeloid leukemia (CML) is a myeloproliferative cancer that is caused by “Philadelphia chromosome” translocation that results in a formation of fusion protein BCR-ABL. This constitutively active tyrosine kinase is necessary and sufficient to cause CML. Several small molecule tyrosine kinase inhibitors (TKI) targeting BCR-ABL kinase activity had been developed and greatly improved CML prognosis. However, significant number of patients develops resistance to TKIs and relapse. Growing evidence shows the importance of other BCR-ABL interaction partners in CML pathogenesis. Precise elucidation of the interactome can lead to design of conceptually new drug targeting different pathways and overcoming TKI resistance. One of our goals is to elucidate precise binding interface among BCR-ABL and it’s “core complex” interaction partners. Our approach involves use of peptide microarrays, which allow us to map the binding interface with single amino acid resolution. Binding motifs discovered in unstructured parts of BCR-ABL can be used to generate synthetic peptide abolishing particular protein interaction. Furthermore, we created large pallet of BCR-ABL deletion/substitution mutants in order to verify interaction boundaries and co-immunoprecipitation experiments have yielded potential new binding sites for some of the core complex interactors.

Druh

O - Ostatní výsledky

CEP obor

—

OECD FORD obor

10608 - Biochemistry and molecular biology

Projekt

Výsledek vznikl pri realizaci vícero projektů. Více informací v záložce Projekty.

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Rok uplatnění

2017

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů