Ghashghaei, Maryam and Liu, Yilin and Ettles, James and Bombaci, Giuseppe and Ramkumar, Niveditha and Liu, Zongmin and Escano, Leo and Miko, Sandra Spencer and Kim, Yerin and Waldron, Joseph A. and Do, Kim and MacPherson, Kyle and Yuen, Katie A. and Taibi, Thilelli and Yue, Marty and Arsalan, Aaremish and Jin, Zhen and Edin, Glenn and Karsan, Aly and Morin, Gregg B. and Kuchenbauer, Florian and Perna, Fabiana and Bushell, Martin and Vu, Ly P. (2024) Translation efficiency driven by CNOT3 subunit of the CCR4-NOT complex promotes leukemogenesis. Nature Communications, 15: 2340. ISSN 2041-1723
AI Summary:
The study uncovers CNOT3, a subunit of the CCR4-NOT complex, as an essential modulator of translation in myeloid leukemia. Elevated CNOT3 expression correlates with unfavorable outcomes in patients with acute myeloid leukemia AML.AI Topics:
Protein synthesis is frequently deregulated during tumorigenesis. However, the precise contexts of selective translational control and the regulators of such mechanisms in cancer is poorly understood. Here, we uncovered CNOT3, a subunit of the CCR4-NOT complex, as an essential modulator of translation in myeloid leukemia. Elevated CNOT3 expression correlates with unfavorable outcomes in patients with acute myeloid leukemia (AML). CNOT3 depletion induces differentiation and apoptosis and delayed leukemogenesis. Transcriptomic and proteomic profiling uncovers c-MYC as a critical downstream target which is translationally regulated by CNOT3. Global analysis of mRNA features demonstrates that CNOT3 selectively influences expression of target genes in a codon usage dependent manner. Furthermore, CNOT3 associates with the protein network largely consisting of ribosomal proteins and translation elongation factors in leukemia cells. Overall, our work elicits the direct requirement for translation efficiency in tumorigenesis and propose targeting the post-transcriptional circuitry via CNOT3 as a therapeutic vulnerability in AML.
Ghashghaei, Maryam
Author
Ghashghaei, Maryam and Liu, Yilin and Ettles, James and Bombaci, Giuseppe and Ramkumar, Niveditha and Liu, Zongmin and Escano, Leo and Miko, Sandra Spencer and Kim, Yerin and Waldron, Joseph A. and Do, Kim and MacPherson, Kyle and Yuen, Katie A. and Taibi, Thilelli and Yue, Marty and Arsalan, Aaremish and Jin, Zhen and Edin, Glenn and Karsan, Aly and Morin, Gregg B. and Kuchenbauer, Florian and Perna, Fabiana and Bushell, Martin and Vu, Ly P. (2024) Translation efficiency driven by CNOT3 subunit of the CCR4-NOT complex promotes leukemogenesis. Nature Communications, 15: 2340. ISSN 2041-1723
See full publications listLiu, Yilin
Author
Ghashghaei, Maryam and Liu, Yilin and Ettles, James and Bombaci, Giuseppe and Ramkumar, Niveditha and Liu, Zongmin and Escano, Leo and Miko, Sandra Spencer and Kim, Yerin and Waldron, Joseph A. and Do, Kim and MacPherson, Kyle and Yuen, Katie A. and Taibi, Thilelli and Yue, Marty and Arsalan, Aaremish and Jin, Zhen and Edin, Glenn and Karsan, Aly and Morin, Gregg B. and Kuchenbauer, Florian and Perna, Fabiana and Bushell, Martin and Vu, Ly P. (2024) Translation efficiency driven by CNOT3 subunit of the CCR4-NOT complex promotes leukemogenesis. Nature Communications, 15: 2340. ISSN 2041-1723
See full publications listEttles, James
Author
Ghashghaei, Maryam and Liu, Yilin and Ettles, James and Bombaci, Giuseppe and Ramkumar, Niveditha and Liu, Zongmin and Escano, Leo and Miko, Sandra Spencer and Kim, Yerin and Waldron, Joseph A. and Do, Kim and MacPherson, Kyle and Yuen, Katie A. and Taibi, Thilelli and Yue, Marty and Arsalan, Aaremish and Jin, Zhen and Edin, Glenn and Karsan, Aly and Morin, Gregg B. and Kuchenbauer, Florian and Perna, Fabiana and Bushell, Martin and Vu, Ly P. (2024) Translation efficiency driven by CNOT3 subunit of the CCR4-NOT complex promotes leukemogenesis. Nature Communications, 15: 2340. ISSN 2041-1723
See full publications listBombaci, Giuseppe
Author
Ghashghaei, Maryam and Liu, Yilin and Ettles, James and Bombaci, Giuseppe and Ramkumar, Niveditha and Liu, Zongmin and Escano, Leo and Miko, Sandra Spencer and Kim, Yerin and Waldron, Joseph A. and Do, Kim and MacPherson, Kyle and Yuen, Katie A. and Taibi, Thilelli and Yue, Marty and Arsalan, Aaremish and Jin, Zhen and Edin, Glenn and Karsan, Aly and Morin, Gregg B. and Kuchenbauer, Florian and Perna, Fabiana and Bushell, Martin and Vu, Ly P. (2024) Translation efficiency driven by CNOT3 subunit of the CCR4-NOT complex promotes leukemogenesis. Nature Communications, 15: 2340. ISSN 2041-1723
See full publications listRamkumar, Niveditha
Author
Ghashghaei, Maryam and Liu, Yilin and Ettles, James and Bombaci, Giuseppe and Ramkumar, Niveditha and Liu, Zongmin and Escano, Leo and Miko, Sandra Spencer and Kim, Yerin and Waldron, Joseph A. and Do, Kim and MacPherson, Kyle and Yuen, Katie A. and Taibi, Thilelli and Yue, Marty and Arsalan, Aaremish and Jin, Zhen and Edin, Glenn and Karsan, Aly and Morin, Gregg B. and Kuchenbauer, Florian and Perna, Fabiana and Bushell, Martin and Vu, Ly P. (2024) Translation efficiency driven by CNOT3 subunit of the CCR4-NOT complex promotes leukemogenesis. Nature Communications, 15: 2340. ISSN 2041-1723
See full publications listLiu, Zongmin
Author
Ghashghaei, Maryam and Liu, Yilin and Ettles, James and Bombaci, Giuseppe and Ramkumar, Niveditha and Liu, Zongmin and Escano, Leo and Miko, Sandra Spencer and Kim, Yerin and Waldron, Joseph A. and Do, Kim and MacPherson, Kyle and Yuen, Katie A. and Taibi, Thilelli and Yue, Marty and Arsalan, Aaremish and Jin, Zhen and Edin, Glenn and Karsan, Aly and Morin, Gregg B. and Kuchenbauer, Florian and Perna, Fabiana and Bushell, Martin and Vu, Ly P. (2024) Translation efficiency driven by CNOT3 subunit of the CCR4-NOT complex promotes leukemogenesis. Nature Communications, 15: 2340. ISSN 2041-1723
See full publications listEscano, Leo
Author
Ghashghaei, Maryam and Liu, Yilin and Ettles, James and Bombaci, Giuseppe and Ramkumar, Niveditha and Liu, Zongmin and Escano, Leo and Miko, Sandra Spencer and Kim, Yerin and Waldron, Joseph A. and Do, Kim and MacPherson, Kyle and Yuen, Katie A. and Taibi, Thilelli and Yue, Marty and Arsalan, Aaremish and Jin, Zhen and Edin, Glenn and Karsan, Aly and Morin, Gregg B. and Kuchenbauer, Florian and Perna, Fabiana and Bushell, Martin and Vu, Ly P. (2024) Translation efficiency driven by CNOT3 subunit of the CCR4-NOT complex promotes leukemogenesis. Nature Communications, 15: 2340. ISSN 2041-1723
See full publications listMiko, Sandra Spencer
Author
Ghashghaei, Maryam and Liu, Yilin and Ettles, James and Bombaci, Giuseppe and Ramkumar, Niveditha and Liu, Zongmin and Escano, Leo and Miko, Sandra Spencer and Kim, Yerin and Waldron, Joseph A. and Do, Kim and MacPherson, Kyle and Yuen, Katie A. and Taibi, Thilelli and Yue, Marty and Arsalan, Aaremish and Jin, Zhen and Edin, Glenn and Karsan, Aly and Morin, Gregg B. and Kuchenbauer, Florian and Perna, Fabiana and Bushell, Martin and Vu, Ly P. (2024) Translation efficiency driven by CNOT3 subunit of the CCR4-NOT complex promotes leukemogenesis. Nature Communications, 15: 2340. ISSN 2041-1723
See full publications listKim, Yerin
Author
Ghashghaei, Maryam and Liu, Yilin and Ettles, James and Bombaci, Giuseppe and Ramkumar, Niveditha and Liu, Zongmin and Escano, Leo and Miko, Sandra Spencer and Kim, Yerin and Waldron, Joseph A. and Do, Kim and MacPherson, Kyle and Yuen, Katie A. and Taibi, Thilelli and Yue, Marty and Arsalan, Aaremish and Jin, Zhen and Edin, Glenn and Karsan, Aly and Morin, Gregg B. and Kuchenbauer, Florian and Perna, Fabiana and Bushell, Martin and Vu, Ly P. (2024) Translation efficiency driven by CNOT3 subunit of the CCR4-NOT complex promotes leukemogenesis. Nature Communications, 15: 2340. ISSN 2041-1723
See full publications listWaldron, Joseph A.
Author
Ghashghaei, Maryam and Liu, Yilin and Ettles, James and Bombaci, Giuseppe and Ramkumar, Niveditha and Liu, Zongmin and Escano, Leo and Miko, Sandra Spencer and Kim, Yerin and Waldron, Joseph A. and Do, Kim and MacPherson, Kyle and Yuen, Katie A. and Taibi, Thilelli and Yue, Marty and Arsalan, Aaremish and Jin, Zhen and Edin, Glenn and Karsan, Aly and Morin, Gregg B. and Kuchenbauer, Florian and Perna, Fabiana and Bushell, Martin and Vu, Ly P. (2024) Translation efficiency driven by CNOT3 subunit of the CCR4-NOT complex promotes leukemogenesis. Nature Communications, 15: 2340. ISSN 2041-1723
See full publications listDo, Kim
Author
Ghashghaei, Maryam and Liu, Yilin and Ettles, James and Bombaci, Giuseppe and Ramkumar, Niveditha and Liu, Zongmin and Escano, Leo and Miko, Sandra Spencer and Kim, Yerin and Waldron, Joseph A. and Do, Kim and MacPherson, Kyle and Yuen, Katie A. and Taibi, Thilelli and Yue, Marty and Arsalan, Aaremish and Jin, Zhen and Edin, Glenn and Karsan, Aly and Morin, Gregg B. and Kuchenbauer, Florian and Perna, Fabiana and Bushell, Martin and Vu, Ly P. (2024) Translation efficiency driven by CNOT3 subunit of the CCR4-NOT complex promotes leukemogenesis. Nature Communications, 15: 2340. ISSN 2041-1723
See full publications listMacPherson, Kyle
Author
Ghashghaei, Maryam and Liu, Yilin and Ettles, James and Bombaci, Giuseppe and Ramkumar, Niveditha and Liu, Zongmin and Escano, Leo and Miko, Sandra Spencer and Kim, Yerin and Waldron, Joseph A. and Do, Kim and MacPherson, Kyle and Yuen, Katie A. and Taibi, Thilelli and Yue, Marty and Arsalan, Aaremish and Jin, Zhen and Edin, Glenn and Karsan, Aly and Morin, Gregg B. and Kuchenbauer, Florian and Perna, Fabiana and Bushell, Martin and Vu, Ly P. (2024) Translation efficiency driven by CNOT3 subunit of the CCR4-NOT complex promotes leukemogenesis. Nature Communications, 15: 2340. ISSN 2041-1723
See full publications listYuen, Katie A.
Author
Ghashghaei, Maryam and Liu, Yilin and Ettles, James and Bombaci, Giuseppe and Ramkumar, Niveditha and Liu, Zongmin and Escano, Leo and Miko, Sandra Spencer and Kim, Yerin and Waldron, Joseph A. and Do, Kim and MacPherson, Kyle and Yuen, Katie A. and Taibi, Thilelli and Yue, Marty and Arsalan, Aaremish and Jin, Zhen and Edin, Glenn and Karsan, Aly and Morin, Gregg B. and Kuchenbauer, Florian and Perna, Fabiana and Bushell, Martin and Vu, Ly P. (2024) Translation efficiency driven by CNOT3 subunit of the CCR4-NOT complex promotes leukemogenesis. Nature Communications, 15: 2340. ISSN 2041-1723
See full publications listTaibi, Thilelli
Author
Ghashghaei, Maryam and Liu, Yilin and Ettles, James and Bombaci, Giuseppe and Ramkumar, Niveditha and Liu, Zongmin and Escano, Leo and Miko, Sandra Spencer and Kim, Yerin and Waldron, Joseph A. and Do, Kim and MacPherson, Kyle and Yuen, Katie A. and Taibi, Thilelli and Yue, Marty and Arsalan, Aaremish and Jin, Zhen and Edin, Glenn and Karsan, Aly and Morin, Gregg B. and Kuchenbauer, Florian and Perna, Fabiana and Bushell, Martin and Vu, Ly P. (2024) Translation efficiency driven by CNOT3 subunit of the CCR4-NOT complex promotes leukemogenesis. Nature Communications, 15: 2340. ISSN 2041-1723
See full publications listYue, Marty
Author
Ghashghaei, Maryam and Liu, Yilin and Ettles, James and Bombaci, Giuseppe and Ramkumar, Niveditha and Liu, Zongmin and Escano, Leo and Miko, Sandra Spencer and Kim, Yerin and Waldron, Joseph A. and Do, Kim and MacPherson, Kyle and Yuen, Katie A. and Taibi, Thilelli and Yue, Marty and Arsalan, Aaremish and Jin, Zhen and Edin, Glenn and Karsan, Aly and Morin, Gregg B. and Kuchenbauer, Florian and Perna, Fabiana and Bushell, Martin and Vu, Ly P. (2024) Translation efficiency driven by CNOT3 subunit of the CCR4-NOT complex promotes leukemogenesis. Nature Communications, 15: 2340. ISSN 2041-1723
See full publications listArsalan, Aaremish
Author
Ghashghaei, Maryam and Liu, Yilin and Ettles, James and Bombaci, Giuseppe and Ramkumar, Niveditha and Liu, Zongmin and Escano, Leo and Miko, Sandra Spencer and Kim, Yerin and Waldron, Joseph A. and Do, Kim and MacPherson, Kyle and Yuen, Katie A. and Taibi, Thilelli and Yue, Marty and Arsalan, Aaremish and Jin, Zhen and Edin, Glenn and Karsan, Aly and Morin, Gregg B. and Kuchenbauer, Florian and Perna, Fabiana and Bushell, Martin and Vu, Ly P. (2024) Translation efficiency driven by CNOT3 subunit of the CCR4-NOT complex promotes leukemogenesis. Nature Communications, 15: 2340. ISSN 2041-1723
See full publications listJin, Zhen
Author
Ghashghaei, Maryam and Liu, Yilin and Ettles, James and Bombaci, Giuseppe and Ramkumar, Niveditha and Liu, Zongmin and Escano, Leo and Miko, Sandra Spencer and Kim, Yerin and Waldron, Joseph A. and Do, Kim and MacPherson, Kyle and Yuen, Katie A. and Taibi, Thilelli and Yue, Marty and Arsalan, Aaremish and Jin, Zhen and Edin, Glenn and Karsan, Aly and Morin, Gregg B. and Kuchenbauer, Florian and Perna, Fabiana and Bushell, Martin and Vu, Ly P. (2024) Translation efficiency driven by CNOT3 subunit of the CCR4-NOT complex promotes leukemogenesis. Nature Communications, 15: 2340. ISSN 2041-1723
See full publications listEdin, Glenn
Author
Ghashghaei, Maryam and Liu, Yilin and Ettles, James and Bombaci, Giuseppe and Ramkumar, Niveditha and Liu, Zongmin and Escano, Leo and Miko, Sandra Spencer and Kim, Yerin and Waldron, Joseph A. and Do, Kim and MacPherson, Kyle and Yuen, Katie A. and Taibi, Thilelli and Yue, Marty and Arsalan, Aaremish and Jin, Zhen and Edin, Glenn and Karsan, Aly and Morin, Gregg B. and Kuchenbauer, Florian and Perna, Fabiana and Bushell, Martin and Vu, Ly P. (2024) Translation efficiency driven by CNOT3 subunit of the CCR4-NOT complex promotes leukemogenesis. Nature Communications, 15: 2340. ISSN 2041-1723
See full publications listKarsan, Aly
Author
Ghashghaei, Maryam and Liu, Yilin and Ettles, James and Bombaci, Giuseppe and Ramkumar, Niveditha and Liu, Zongmin and Escano, Leo and Miko, Sandra Spencer and Kim, Yerin and Waldron, Joseph A. and Do, Kim and MacPherson, Kyle and Yuen, Katie A. and Taibi, Thilelli and Yue, Marty and Arsalan, Aaremish and Jin, Zhen and Edin, Glenn and Karsan, Aly and Morin, Gregg B. and Kuchenbauer, Florian and Perna, Fabiana and Bushell, Martin and Vu, Ly P. (2024) Translation efficiency driven by CNOT3 subunit of the CCR4-NOT complex promotes leukemogenesis. Nature Communications, 15: 2340. ISSN 2041-1723
See full publications listMorin, Gregg B.
Author
Ghashghaei, Maryam and Liu, Yilin and Ettles, James and Bombaci, Giuseppe and Ramkumar, Niveditha and Liu, Zongmin and Escano, Leo and Miko, Sandra Spencer and Kim, Yerin and Waldron, Joseph A. and Do, Kim and MacPherson, Kyle and Yuen, Katie A. and Taibi, Thilelli and Yue, Marty and Arsalan, Aaremish and Jin, Zhen and Edin, Glenn and Karsan, Aly and Morin, Gregg B. and Kuchenbauer, Florian and Perna, Fabiana and Bushell, Martin and Vu, Ly P. (2024) Translation efficiency driven by CNOT3 subunit of the CCR4-NOT complex promotes leukemogenesis. Nature Communications, 15: 2340. ISSN 2041-1723
See full publications listKuchenbauer, Florian
Author
Ghashghaei, Maryam and Liu, Yilin and Ettles, James and Bombaci, Giuseppe and Ramkumar, Niveditha and Liu, Zongmin and Escano, Leo and Miko, Sandra Spencer and Kim, Yerin and Waldron, Joseph A. and Do, Kim and MacPherson, Kyle and Yuen, Katie A. and Taibi, Thilelli and Yue, Marty and Arsalan, Aaremish and Jin, Zhen and Edin, Glenn and Karsan, Aly and Morin, Gregg B. and Kuchenbauer, Florian and Perna, Fabiana and Bushell, Martin and Vu, Ly P. (2024) Translation efficiency driven by CNOT3 subunit of the CCR4-NOT complex promotes leukemogenesis. Nature Communications, 15: 2340. ISSN 2041-1723
See full publications listPerna, Fabiana
Author
Ghashghaei, Maryam and Liu, Yilin and Ettles, James and Bombaci, Giuseppe and Ramkumar, Niveditha and Liu, Zongmin and Escano, Leo and Miko, Sandra Spencer and Kim, Yerin and Waldron, Joseph A. and Do, Kim and MacPherson, Kyle and Yuen, Katie A. and Taibi, Thilelli and Yue, Marty and Arsalan, Aaremish and Jin, Zhen and Edin, Glenn and Karsan, Aly and Morin, Gregg B. and Kuchenbauer, Florian and Perna, Fabiana and Bushell, Martin and Vu, Ly P. (2024) Translation efficiency driven by CNOT3 subunit of the CCR4-NOT complex promotes leukemogenesis. Nature Communications, 15: 2340. ISSN 2041-1723
See full publications listBushell, Martin
Author
Dearlove, Emily L. and Chatrin, Chatrin and Buetow, Lori and Ahmed, Syed F. and Schmidt, Tobias and Bushell, Martin and Smith, Brian O. and Huang, Danny T. (2024) DTX3L ubiquitin ligase ubiquitinates single-stranded nucleic acids. eLife, 13: RP98070. ISSN 2050-084X
Ghashghaei, Maryam and Liu, Yilin and Ettles, James and Bombaci, Giuseppe and Ramkumar, Niveditha and Liu, Zongmin and Escano, Leo and Miko, Sandra Spencer and Kim, Yerin and Waldron, Joseph A. and Do, Kim and MacPherson, Kyle and Yuen, Katie A. and Taibi, Thilelli and Yue, Marty and Arsalan, Aaremish and Jin, Zhen and Edin, Glenn and Karsan, Aly and Morin, Gregg B. and Kuchenbauer, Florian and Perna, Fabiana and Bushell, Martin and Vu, Ly P. (2024) Translation efficiency driven by CNOT3 subunit of the CCR4-NOT complex promotes leukemogenesis. Nature Communications, 15: 2340. ISSN 2041-1723
See full publications listVu, Ly P.
Author
Ghashghaei, Maryam and Liu, Yilin and Ettles, James and Bombaci, Giuseppe and Ramkumar, Niveditha and Liu, Zongmin and Escano, Leo and Miko, Sandra Spencer and Kim, Yerin and Waldron, Joseph A. and Do, Kim and MacPherson, Kyle and Yuen, Katie A. and Taibi, Thilelli and Yue, Marty and Arsalan, Aaremish and Jin, Zhen and Edin, Glenn and Karsan, Aly and Morin, Gregg B. and Kuchenbauer, Florian and Perna, Fabiana and Bushell, Martin and Vu, Ly P. (2024) Translation efficiency driven by CNOT3 subunit of the CCR4-NOT complex promotes leukemogenesis. Nature Communications, 15: 2340. ISSN 2041-1723
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