Systematic analysis of BCR-ABL interactome in chronic myeloid
leukemia

a 2017

Systematic analysis of BCR-ABL interactome in chronic myeloid leukemia

GREGOR, Tomáš, Jan RYNEŠ, Silvie TRANTÍRKOVÁ, Jiří MAYER, Pavel KREJČÍ et. al.

Basic information

Original name

Systematic analysis of BCR-ABL interactome in chronic myeloid leukemia

Authors

GREGOR, Tomáš (203 Czech Republic, belonging to the institution), Jan RYNEŠ (203 Czech Republic, belonging to the institution), Silvie TRANTÍRKOVÁ (203 Czech Republic, belonging to the institution), Jiří MAYER (203 Czech Republic, belonging to the institution), Pavel KREJČÍ (203 Czech Republic, belonging to the institution) and Lukáš TRANTÍREK (203 Czech Republic, belonging to the institution)

Edition

42nd Congress of the Federation-of-European-Biochemical-Societies (FEBS) on From Molecules to Cells and Back, 2017

Other information

Language

English

Type of outcome

Konferenční abstrakt

Field of Study

10608 Biochemistry and molecular biology

Confidentiality degree

není předmětem státního či obchodního tajemství

References:

URL

Impact factor

Impact factor: 4.530

RIV identification code

RIV/00216224:14740/17:00095713

Organization unit

Central European Institute of Technology

ISSN

UT WoS

000409918903263

Keywords in English

BCR-ABL; chronic myeloid leukemia

Abstract

V originále

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.

Links

LQ1601, research and development project

Name: CEITEC 2020 (Acronym: CEITEC2020)

Investor: Ministry of Education, Youth and Sports of the CR

NV15-33232A, research and development project

Name: Identifikace nových možností léčby achondroplásie prostřednictvím analýzy interakce FGFR3 a adaptérového proteinu Frs2

NV15-34405A, research and development project

Name: Identifikace nových možností léčby chronické myeloidní leukémie pomocí systematické analýzy interaktomu proteinu BCR-ABL

Citovat

GREGOR, Tomáš, Jan RYNEŠ, Silvie TRANTÍRKOVÁ, Jiří MAYER, Pavel KREJČÍ and Lukáš TRANTÍREK. Systematic analysis of BCR-ABL interactome in chronic myeloid leukemia. In 42nd Congress of the Federation-of-European-Biochemical-Societies (FEBS) on From Molecules to Cells and Back. 2017. ISSN 1742-464X.

@proceedings{1411821,
   author = {Gregor, Tomáš and Ryneš, Jan and Trantírková, Silvie and Mayer, Jiří and Krejčí, Pavel and Trantírek, Lukáš},
   booktitle = {42nd Congress of the Federation-of-European-Biochemical-Societies (FEBS) on From Molecules to Cells and Back},
   keywords = {BCR-ABL; chronic myeloid leukemia},
   language = {eng},
   title = {Systematic analysis of BCR-ABL interactome in chronic myeloid leukemia},
   url = {https://2017.febscongress.org/abstract_preview.aspx?idAbstractEnc=4424170093097092096093424170},
   year = {2017}
}

TY  - CONF
ID  - 1411821
AU  - Gregor, Tomáš - Ryneš, Jan - Trantírková, Silvie - Mayer, Jiří - Krejčí, Pavel - Trantírek, Lukáš
PY  - 2017
TI  - Systematic analysis of BCR-ABL interactome in chronic myeloid leukemia
KW  - BCR-ABL
KW  - chronic myeloid leukemia
UR  - https://2017.febscongress.org/abstract_preview.aspx?idAbstractEnc=4424170093097092096093424170
L2  - https://2017.febscongress.org/abstract_preview.aspx?idAbstractEnc=4424170093097092096093424170
N2  - 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.
ER  -

GREGOR, Tomáš, Jan RYNEŠ, Silvie TRANTÍRKOVÁ, Jiří MAYER, Pavel KREJČÍ and Lukáš TRANTÍREK. Systematic analysis of BCR-ABL interactome in chronic myeloid leukemia. In \textit{42nd Congress of the Federation-of-European-Biochemical-Societies (FEBS) on From Molecules to Cells and Back}. 2017. ISSN~1742-464X.

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