Elucidation of protein interactions necessary for the
maintenance of the BCR-ABL signaling complex

J 2020

Elucidation of protein interactions necessary for the maintenance of the BCR-ABL signaling complex

GREGOR, Tomáš, Michaela BOSÁKOVÁ, Alexandru NITĂ, Sara POOVAKULATHU ABRAHAM, Bohumil FAFÍLEK et. al.

Basic information

Original name

Elucidation of protein interactions necessary for the maintenance of the BCR-ABL signaling complex

Authors

GREGOR, Tomáš (203 Czech Republic, belonging to the institution), Michaela BOSÁKOVÁ (203 Czech Republic, belonging to the institution), Alexandru NITĂ (642 Romania, belonging to the institution), Sara POOVAKULATHU ABRAHAM (356 India, belonging to the institution), Bohumil FAFÍLEK (203 Czech Republic, belonging to the institution), Nicole ČERNOHORSKÁ (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), Daniela ŽÁČKOVÁ (203 Czech Republic, belonging to the institution), Jiří MAYER (203 Czech Republic, belonging to the institution), Lukáš TRANTÍREK (203 Czech Republic, belonging to the institution) and Pavel KREJČÍ (203 Czech Republic, guarantor, belonging to the institution)

Edition

Cellular and molecular life sciences, BASEL, SPRINGER BASEL AG, 2020, 1420-682X

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

10608 Biochemistry and molecular biology

Country of publisher

Switzerland

Confidentiality degree

není předmětem státního či obchodního tajemství

References:

URL

Impact factor

Impact factor: 9.261

RIV identification code

RIV/00216224:14110/20:00116512

Organization unit

Faculty of Medicine

DOI

http://dx.doi.org/10.1007/s00018-019-03397-7

UT WoS

000566036300001

Keywords in English

BCR-ABL; Chronic myeloid leukemia; Signaling; Protein complex

Abstract

V originále

Many patients with chronic myeloid leukemia in deep remission experience return of clinical disease after withdrawal of tyrosine kinase inhibitors (TKIs). This suggests signaling of inactive BCR-ABL, which allows the survival of cancer cells, and relapse. We show that TKI treatment inhibits catalytic activity of BCR-ABL, but does not dissolve BCR-ABL core signaling complex, consisting of CRKL, SHC1, GRB2, SOS1, cCBL, p85a-PI3K, STS1 and SHIP2. Peptide microarray and co-immunoprecipitation results demonstrate that CRKL binds to proline-rich regions located in C-terminal, intrinsically disordered region of BCR-ABL, that SHC1 requires pleckstrin homology, src homology and tyrosine kinase domains of BCR-ABL for binding, and that BCR-ABL sequence motif located in disordered region around phosphorylated tyrosine 177 mediates binding of three core complex members, i.e., GRB2, SOS1, and cCBL. Further, SHIP2 binds to the src homology and tyrosine kinase domains of BCR-ABL and its inositol phosphatase activity contributes to BCR-ABL-mediated phosphorylation of SHC1. Together, this study characterizes protein-protein interactions within the BCR-ABL core complex and determines the contribution of particular BCR-ABL domains to downstream signaling. Understanding the structure and dynamics of BCR-ABL interactome is critical for the development of drugs targeting integrity of the BCR-ABL core complex.

Links

LM2018128, research and development project

Name: Český národní uzel Evropské sítě infrastruktur klinického výzkumu (Acronym: CZECRIN)

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

MUNI/A/0951/2019, interní kód MU

Name: Buněčná a molekulární biologie pro Biomedicínské vědy

Investor: Masaryk University, Category A

NV15-34405A, research and development project

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

Citovat

GREGOR, Tomáš, Michaela BOSÁKOVÁ, Alexandru NITĂ, Sara POOVAKULATHU ABRAHAM, Bohumil FAFÍLEK, Nicole ČERNOHORSKÁ, Jan RYNEŠ, Silvie TRANTÍRKOVÁ, Daniela ŽÁČKOVÁ, Jiří MAYER, Lukáš TRANTÍREK and Pavel KREJČÍ. Elucidation of protein interactions necessary for the maintenance of the BCR-ABL signaling complex. Cellular and molecular life sciences. BASEL: SPRINGER BASEL AG, 2020, vol. 77, No 19, p. 3885-3903. ISSN 1420-682X. Available from: https://dx.doi.org/10.1007/s00018-019-03397-7.

@article{1681537,
   author = {Gregor, Tomáš and Bosáková, Michaela and Nită, Alexandru and Poovakulathu Abraham, Sara and Fafílek, Bohumil and Černohorská, Nicole and Ryneš, Jan and Trantírková, Silvie and Žáčková, Daniela and Mayer, Jiří and Trantírek, Lukáš and Krejčí, Pavel},
   article_location = {BASEL},
   article_number = {19},
   doi = {http://dx.doi.org/10.1007/s00018-019-03397-7},
   keywords = {BCR-ABL; Chronic myeloid leukemia; Signaling; Protein complex},
   language = {eng},
   issn = {1420-682X},
   journal = {Cellular and molecular life sciences},
   title = {Elucidation of protein interactions necessary for the maintenance of the BCR-ABL signaling complex},
   url = {https://link.springer.com/article/10.1007/s00018-019-03397-7},
   volume = {77},
   year = {2020}
}

TY  - JOUR
ID  - 1681537
AU  - Gregor, Tomáš - Bosáková, Michaela - Nită, Alexandru - Poovakulathu Abraham, Sara - Fafílek, Bohumil - Černohorská, Nicole - Ryneš, Jan - Trantírková, Silvie - Žáčková, Daniela - Mayer, Jiří - Trantírek, Lukáš - Krejčí, Pavel
PY  - 2020
TI  - Elucidation of protein interactions necessary for the maintenance of the BCR-ABL signaling complex
JF  - Cellular and molecular life sciences
VL  - 77
IS  - 19
SP  - 3885-3903
EP  - 3885-3903
PB  - SPRINGER BASEL AG
SN  - 1420682X
KW  - BCR-ABL
KW  - Chronic myeloid leukemia
KW  - Signaling
KW  - Protein complex
UR  - https://link.springer.com/article/10.1007/s00018-019-03397-7
L2  - https://link.springer.com/article/10.1007/s00018-019-03397-7
N2  - Many patients with chronic myeloid leukemia in deep remission experience return of clinical disease after withdrawal of tyrosine kinase inhibitors (TKIs). This suggests signaling of inactive BCR-ABL, which allows the survival of cancer cells, and relapse. We show that TKI treatment inhibits catalytic activity of BCR-ABL, but does not dissolve BCR-ABL core signaling complex, consisting of CRKL, SHC1, GRB2, SOS1, cCBL, p85a-PI3K, STS1 and SHIP2. Peptide microarray and co-immunoprecipitation results demonstrate that CRKL binds to proline-rich regions located in C-terminal, intrinsically disordered region of BCR-ABL, that SHC1 requires pleckstrin homology, src homology and tyrosine kinase domains of BCR-ABL for binding, and that BCR-ABL sequence motif located in disordered region around phosphorylated tyrosine 177 mediates binding of three core complex members, i.e., GRB2, SOS1, and cCBL. Further, SHIP2 binds to the src homology and tyrosine kinase domains of BCR-ABL and its inositol phosphatase activity contributes to BCR-ABL-mediated phosphorylation of SHC1. Together, this study characterizes protein-protein interactions within the BCR-ABL core complex and determines the contribution of particular BCR-ABL domains to downstream signaling. Understanding the structure and dynamics of BCR-ABL interactome is critical for the development of drugs targeting integrity of the BCR-ABL core complex.
ER  -

GREGOR, Tomáš, Michaela BOSÁKOVÁ, Alexandru NIT$\backslash$U A, Sara POOVAKULATHU ABRAHAM, Bohumil FAFÍLEK, Nicole ČERNOHORSKÁ, Jan RYNEŠ, Silvie TRANTÍRKOVÁ, Daniela ŽÁČKOVÁ, Jiří MAYER, Lukáš TRANTÍREK and Pavel KREJČÍ. Elucidation of protein interactions necessary for the maintenance of the BCR-ABL signaling complex. \textit{Cellular and molecular life sciences}. BASEL: SPRINGER BASEL AG, 2020, vol.~77, No~19, p.~3885-3903. ISSN~1420-682X. Available from: https://dx.doi.org/10.1007/s00018-019-03397-7.

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