Matches in SemOpenAlex for { <https://semopenalex.org/work/W3037822706> ?p ?o ?g. }
- W3037822706 abstract "ABSTRACT SF3B1 is the most frequently mutated RNA splicing factor in multiple neoplasms, including ~25% of myelodysplastic syndromes (MDS) patients. Mortality in MDS frequently results from severe anemia, but the underlying mechanism is largely unknown. Here we elucidate the detailed, elusive pathway by which SF3B1 mutations cause anemia. We demonstrate, in CRISPR-edited cell models, normal human primary cells, and MDS patient cells, that mutant SF3B1 induces a splicing error in transcripts encoding the kinase MAP3K7, resulting in reduced MAP3K7 protein levels and deactivation of downstream target p38 MAPK. We show that disruption of this MAP3K7-p38 MAPK pathway leads to premature downregulation of GATA1, a master regulator of erythroid differentiation, and that this is sufficient to trigger accelerated differentiation and apoptosis. As a result, the overproduced, late staged erythroblasts undergo apoptosis and are unable to mature in the bone marrow. Our findings provide a detailed mechanism explaining the origins of anemia in MDS patients harboring SF3B1 mutations." @default.
- W3037822706 created "2020-07-02" @default.
- W3037822706 creator A5000060206 @default.
- W3037822706 creator A5008056393 @default.
- W3037822706 creator A5028632049 @default.
- W3037822706 creator A5033415932 @default.
- W3037822706 creator A5041886191 @default.
- W3037822706 creator A5042844951 @default.
- W3037822706 creator A5056128255 @default.
- W3037822706 creator A5059343631 @default.
- W3037822706 creator A5083528886 @default.
- W3037822706 creator A5087963156 @default.
- W3037822706 creator A5089932855 @default.
- W3037822706 date "2020-06-26" @default.
- W3037822706 modified "2023-10-16" @default.
- W3037822706 title "SF3B1 mutant-induced missplicing of MAP3K7 causes anemia in myelodysplastic syndromes" @default.
- W3037822706 cites W1891216743 @default.
- W3037822706 cites W1915661113 @default.
- W3037822706 cites W1930624773 @default.
- W3037822706 cites W1966203663 @default.
- W3037822706 cites W1967997373 @default.
- W3037822706 cites W1974371672 @default.
- W3037822706 cites W1978538135 @default.
- W3037822706 cites W1979233636 @default.
- W3037822706 cites W1990288371 @default.
- W3037822706 cites W1999516852 @default.
- W3037822706 cites W2001838080 @default.
- W3037822706 cites W2004668804 @default.
- W3037822706 cites W2005150790 @default.
- W3037822706 cites W2005293659 @default.
- W3037822706 cites W2011211995 @default.
- W3037822706 cites W2013277487 @default.
- W3037822706 cites W2013898117 @default.
- W3037822706 cites W2023843593 @default.
- W3037822706 cites W2030364523 @default.
- W3037822706 cites W2031385635 @default.
- W3037822706 cites W2048282457 @default.
- W3037822706 cites W2048719634 @default.
- W3037822706 cites W2053503772 @default.
- W3037822706 cites W2054962683 @default.
- W3037822706 cites W2057137292 @default.
- W3037822706 cites W2064792481 @default.
- W3037822706 cites W2065401691 @default.
- W3037822706 cites W2066960428 @default.
- W3037822706 cites W2073889874 @default.
- W3037822706 cites W2075086833 @default.
- W3037822706 cites W2077274633 @default.
- W3037822706 cites W2098550012 @default.
- W3037822706 cites W2099411992 @default.
- W3037822706 cites W2100438302 @default.
- W3037822706 cites W2127054377 @default.
- W3037822706 cites W2140419897 @default.
- W3037822706 cites W2144892629 @default.
- W3037822706 cites W2145842706 @default.
- W3037822706 cites W2146652917 @default.
- W3037822706 cites W2149848093 @default.
- W3037822706 cites W2151462466 @default.
- W3037822706 cites W2153482452 @default.
- W3037822706 cites W2170233852 @default.
- W3037822706 cites W2179829063 @default.
- W3037822706 cites W2193225046 @default.
- W3037822706 cites W2278285517 @default.
- W3037822706 cites W2278976048 @default.
- W3037822706 cites W2300220838 @default.
- W3037822706 cites W2313011831 @default.
- W3037822706 cites W2401903257 @default.
- W3037822706 cites W2413340136 @default.
- W3037822706 cites W2511911618 @default.
- W3037822706 cites W2520178460 @default.
- W3037822706 cites W2546500680 @default.
- W3037822706 cites W2551607099 @default.
- W3037822706 cites W2560246503 @default.
- W3037822706 cites W2589206684 @default.
- W3037822706 cites W2790231673 @default.
- W3037822706 cites W2795877840 @default.
- W3037822706 cites W2808443795 @default.
- W3037822706 cites W2808716448 @default.
- W3037822706 cites W2887459058 @default.
- W3037822706 cites W2895193914 @default.
- W3037822706 cites W2898100044 @default.
- W3037822706 cites W2913402023 @default.
- W3037822706 cites W2957476816 @default.
- W3037822706 cites W2971269466 @default.
- W3037822706 cites W2980036112 @default.
- W3037822706 cites W3719606 @default.
- W3037822706 cites W4232645703 @default.
- W3037822706 doi "https://doi.org/10.1101/2020.06.24.169052" @default.
- W3037822706 hasPublicationYear "2020" @default.
- W3037822706 type Work @default.
- W3037822706 sameAs 3037822706 @default.
- W3037822706 citedByCount "2" @default.
- W3037822706 countsByYear W30378227062020 @default.
- W3037822706 crossrefType "posted-content" @default.
- W3037822706 hasAuthorship W3037822706A5000060206 @default.
- W3037822706 hasAuthorship W3037822706A5008056393 @default.
- W3037822706 hasAuthorship W3037822706A5028632049 @default.
- W3037822706 hasAuthorship W3037822706A5033415932 @default.
- W3037822706 hasAuthorship W3037822706A5041886191 @default.
- W3037822706 hasAuthorship W3037822706A5042844951 @default.
- W3037822706 hasAuthorship W3037822706A5056128255 @default.