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245 1 0 _aPhase separation-competent FBL promotes early pre-rRNA processing and translation in acute myeloid leukaemia.
490 0 _aNature Cell Biology, 26(6), 946-961, 2024.
500 _aArtículo
520 3 _aRNA-binding proteins (RBPs) are pivotal in acute myeloid leukaemia (AML), a lethal disease. Although specific phase separation-competent RBPs are recognized in AML, the effect of their condensate formation on AML leukaemogenesis, and the therapeutic potential of inhibition of phase separation are underexplored. In our in vivo CRISPR RBP screen, fibrillarin (FBL) emerges as a crucial nucleolar protein that regulates AML cell survival, primarily through its phase separation domains rather than methyltransferase or acetylation domains. These phase separation domains, with specific features, coordinately drive nucleoli formation and early processing of pre-rRNA (including efflux, cleavage and methylation), eventually enhancing the translation of oncogenes such as MYC. Targeting the phase separation capability of FBL with CGX-635 leads to elimination of AML cells, suggesting an additional mechanism of action for CGX-635 that complements its established therapeutic effects. We highlight the potential of PS modulation of critical proteins as a possible therapeutic strategy for AML.
650 1 4 _aCRISPR ASSOCIATED PROTEIN
650 1 4 _aFIBRILLARIN
650 1 4 _aFLUOROURACIL
650 1 4 _aHOMOHARRINGTONINE
650 1 4 _aMETHYLTRANSFERASE
650 1 4 _aMYC PROTEIN
650 1 4 _aRIBOSOME RNA
650 1 4 _aRNA BINDING PROTEIN
650 1 4 _aFIBRILLARIN
650 1 4 _aNONHISTONE PROTEIN
650 1 4 _aRNA BINDING PROTEIN
700 1 2 _aYang, L.
700 1 2 _aZhang, Z.
700 1 2 _aJiang, P.
700 1 2 _aKong, D.
700 1 2 _aYu, Z.
700 1 2 _aShi, D.
700 1 2 _aQian, P.
856 4 0 _uhttps://drive.google.com/file/d/1kROz1IsTFFBygfRQ-Vr05ybWW7BZJbKS/view?usp=drive_link
_zPara ver el documento ingresa a Google con tu cuenta: @cicy.edu.mx
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