Sequential inverse dysregulation of the RNA helicases DDX3X and
DDX3Y facilitates MYC-driven lymphomagenesis

J 2021

Sequential inverse dysregulation of the RNA helicases DDX3X and DDX3Y facilitates MYC-driven lymphomagenesis

GONG, C.; J.A. KRUPKA; J. GAO; N.F. GRIGOROPOULOS; G. GIOTOPOULOS et al.

Základní údaje

Originální název

Sequential inverse dysregulation of the RNA helicases DDX3X and DDX3Y facilitates MYC-driven lymphomagenesis

Autoři

Vydání

Molecular Cell, CAMBRIDGE, CELL PRESS, 2021, 1097-2765

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

10608 Biochemistry and molecular biology

Stát vydavatele

Spojené státy

Utajení

není předmětem státního či obchodního tajemství

Odkazy

URL

Impakt faktor

Impact factor: 19.328

Označené pro přenos do RIV

Ano

Kód RIV

RIV/00216224:14740/21:00124253

Organizační jednotka

Středoevropský technologický institut

Klíčová slova anglicky

AZFA GENE DDX3Y; MESSENGER-RNA; TUMOR-SUPPRESSOR; STRESS GRANULES; READ ALIGNMENT; EEF2 KINASE; TRANSLATION; PROTEIN; MUTATIONS; IDENTIFICATIONAZFA GENE DDX3Y; MESSENGER-RNA; TUMOR-SUPPRESSOR

Štítky

rivok

Příznaky

Mezinárodní význam, Recenzováno

Změněno: 22. 2. 2022 17:31, Mgr. Pavla Foltynová, Ph.D.

Anotace

V originále

DDX3X is a ubiquitously expressed RNA helicase involved in multiple stages of RNA biogenesis. DDX3X is frequently mutated in Burkitt lymphoma, but the functional basis for this is unknown. Here, we show that loss-of-function DDX3X mutations are also enriched in MYC-translocated diffuse large B cell lymphoma and reveal functional cooperation between mutant DDX3X and MYC. DDX3X promotes the translation of mRNA encoding components of the core translational machinery, thereby driving global protein synthesis. Loss-of-function DDX3X mutations moderate MYC-driven global protein synthesis, thereby buffering MYC-induced proteotoxic stress during early lymphomagenesis. Established lymphoma cells restore full protein synthetic capacity by aberrant expression of DDX3Y, a Y chromosome homolog, the expression of which is normally restricted to the testis. These findings show that DDX3X loss of function can buffer MYC-driven proteotoxic stress and highlight the capacity of male B cell lymphomas to then compensate for this loss by ectopic DDX3Y expression.

Citovat

GONG, C.; J.A. KRUPKA; J. GAO; N.F. GRIGOROPOULOS; G. GIOTOPOULOS; R. ASBY; M. SCREEN; Z. USHEVA; F. CUCCO; S. BARRANS; D. PAINTER; N.B.M. ZAINI; B. HAUPL; S. BORNELOV; I.R. DE LOS MOZOS; W. MENG; P.X. ZHOU; A.E. BLAIN; S. FORDE; J. MATTHEWS; M.G.K. TAN; G.A.A. BURKE; S.K. SZE; P. BEER; C. BURTON; P. CAMPBELL; V. RAND; Suzanne Dawn TURNER; J. ULE; E. ROMAN; R. TOOZE; T. OELLERICH; B.J. HUNTLY; M. TURNER; M.Q. DU; S.A. SAMARAJIWA a D.J. HODSON. Sequential inverse dysregulation of the RNA helicases DDX3X and DDX3Y facilitates MYC-driven lymphomagenesis. Molecular Cell. CAMBRIDGE: CELL PRESS, 2021, roč. 81, č. 19, s. "4059"-"+", 29 s. ISSN 1097-2765. Dostupné z: https://doi.org/10.1016/j.molcel.2021.07.041.

@article{1836432,
   author = {Gong, C. and Krupka, J.A. and Gao, J. and Grigoropoulos, N.F. and Giotopoulos, G. and Asby, R. and Screen, M. and Usheva, Z. and Cucco, F. and Barrans, S. and Painter, D. and Zaini, N.B.M. and Haupl, B. and Bornelov, S. and De Los Mozos, I.R. and Meng, W. and Zhou, P.X. and Blain, A.E. and Forde, S. and Matthews, J. and Tan, M.G.K. and Burke, G.A.A. and Sze, S.K. and Beer, P. and Burton, C. and Campbell, P. and Rand, V. and Turner, Suzanne Dawn and Ule, J. and Roman, E. and Tooze, R. and Oellerich, T. and Huntly, B.J. and Turner, M. and Du, M.Q. and Samarajiwa, S.A. and Hodson, D.J.},
   article_location = {CAMBRIDGE},
   article_number = {19},
   doi = {https://doi.org/10.1016/j.molcel.2021.07.041},
   keywords = {AZFA GENE DDX3Y; MESSENGER-RNA; TUMOR-SUPPRESSOR; STRESS GRANULES; READ ALIGNMENT; EEF2 KINASE; TRANSLATION; PROTEIN; MUTATIONS; IDENTIFICATIONAZFA GENE DDX3Y; MESSENGER-RNA; TUMOR-SUPPRESSOR},
   language = {eng},
   issn = {1097-2765},
   journal = {Molecular Cell},
   title = {Sequential inverse dysregulation of the RNA helicases DDX3X and DDX3Y facilitates MYC-driven lymphomagenesis},
   url = {https://www.sciencedirect.com/science/article/pii/S1097276521006250?via%3Dihub},
   volume = {81},
   year = {2021}
}

TY  - JOUR
ID  - 1836432
AU  - Gong, C. - Krupka, J.A. - Gao, J. - Grigoropoulos, N.F. - Giotopoulos, G. - Asby, R. - Screen, M. - Usheva, Z. - Cucco, F. - Barrans, S. - Painter, D. - Zaini, N.B.M. - Haupl, B. - Bornelov, S. - De Los Mozos, I.R. - Meng, W. - Zhou, P.X. - Blain, A.E. - Forde, S. - Matthews, J. - Tan, M.G.K. - Burke, G.A.A. - Sze, S.K. - Beer, P. - Burton, C. - Campbell, P. - Rand, V. - Turner, Suzanne Dawn - Ule, J. - Roman, E. - Tooze, R. - Oellerich, T. - Huntly, B.J. - Turner, M. - Du, M.Q. - Samarajiwa, S.A. - Hodson, D.J.
PY  - 2021
TI  - Sequential inverse dysregulation of the RNA helicases DDX3X and DDX3Y facilitates MYC-driven lymphomagenesis
JF  - Molecular Cell
VL  - 81
IS  - 19
SP  - "4059"-"+"
EP  - "4059"-"+"
PB  - CELL PRESS
SN  - 10972765
KW  - AZFA GENE DDX3Y
KW  - MESSENGER-RNA
KW  - TUMOR-SUPPRESSOR
KW  - STRESS GRANULES
KW  - READ ALIGNMENT
KW  - EEF2 KINASE
KW  - TRANSLATION
KW  - PROTEIN
KW  - MUTATIONS
KW  - IDENTIFICATIONAZFA GENE DDX3Y
KW  - MESSENGER-RNA
KW  - TUMOR-SUPPRESSOR
UR  - https://www.sciencedirect.com/science/article/pii/S1097276521006250?via%3Dihub
N2  - DDX3X is a ubiquitously expressed RNA helicase involved in multiple stages of RNA biogenesis. DDX3X is frequently mutated in Burkitt lymphoma, but the functional basis for this is unknown. Here, we show that loss-of-function DDX3X mutations are also enriched in MYC-translocated diffuse large B cell lymphoma and reveal functional cooperation between mutant DDX3X and MYC. DDX3X promotes the translation of mRNA encoding components of the core translational machinery, thereby driving global protein synthesis. Loss-of-function DDX3X mutations moderate MYC-driven global protein synthesis, thereby buffering MYC-induced proteotoxic stress during early lymphomagenesis. Established lymphoma cells restore full protein synthetic capacity by aberrant expression of DDX3Y, a Y chromosome homolog, the expression of which is normally restricted to the testis. These findings show that DDX3X loss of function can buffer MYC-driven proteotoxic stress and highlight the capacity of male B cell lymphomas to then compensate for this loss by ectopic DDX3Y expression.
ER  -

GONG, C.; J.A. KRUPKA; J. GAO; N.F. GRIGOROPOULOS; G. GIOTOPOULOS; R. ASBY; M. SCREEN; Z. USHEVA; F. CUCCO; S. BARRANS; D. PAINTER; N.B.M. ZAINI; B. HAUPL; S. BORNELOV; I.R. DE LOS MOZOS; W. MENG; P.X. ZHOU; A.E. BLAIN; S. FORDE; J. MATTHEWS; M.G.K. TAN; G.A.A. BURKE; S.K. SZE; P. BEER; C. BURTON; P. CAMPBELL; V. RAND; Suzanne Dawn TURNER; J. ULE; E. ROMAN; R. TOOZE; T. OELLERICH; B.J. HUNTLY; M. TURNER; M.Q. DU; S.A. SAMARAJIWA a D.J. HODSON. Sequential inverse dysregulation of the RNA helicases DDX3X and DDX3Y facilitates MYC-driven lymphomagenesis. \textit{Molecular Cell}. CAMBRIDGE: CELL PRESS, 2021, roč.~81, č.~19, s.~''4059''-''+'', 29 s. ISSN~1097-2765. Dostupné z: https://doi.org/10.1016/j.molcel.2021.07.041.

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