Core binding factor 13 (CBF,B) is considered to be a transcriptional coactivator that dimerizes with transcription factors core binding factor a 1 (CBFA1), -2, and -3, and enhances DNA binding capacity of these transcription factors. CBFI3 and CBFA2, which is also called acute myeloid leukemia 1 gene, are frequently involved in chromosomal translocations in human leukemia. To elucidate the function of CBFP, mice carrying a mutation in the Cbfb locus were
The human ATP-binding cassette (ABC) transporter ABCB6 has been described as a mitochondrial porphyrin transporter essential for heme biosynthesis1, but is also suspected to contribute to anticancer drug resistance2–4, as do other ABC transporters located at the plasma membrane. We identified ABCB6 as the carrier of the blood group antigen Lan on red blood cells, but also at the plasma membrane of hepatocellular carcinoma (HCC) cells, and established that ABCB6 actually encodes a new blood group system (Langereis, Lan). Targeted sequencing of ABCB6 in 12 unrelated individuals of the blood type Lan− identified 10 different ABCB6 null mutations. This is the first report of deficient alleles of this human ABC transporter gene. Surprisingly, Lan− (ABCB6−/−) individuals do not suffer any clinical consequences, albeit their deficiency in ABCB6 may place them at risk when defining drug dosage.
Efforts to identify host determinants for malaria have been hindered by the absence of a nucleus in erythrocytes, precluding genetic manipulation in the cell where the parasite replicates. We used cultured red blood cells derived from hematopoietic stem cells to carry out a forward genetic screen for Plasmodium falciparum host determinants. We found that CD55 is an essential host factor for P. falciparum invasion. CD55-null erythrocytes were refractory to invasion by all isolates of P. falciparum because parasites failed to attach properly to the erythrocyte surface. Thus, CD55 is an attractive target for the development of malaria therapeutics. Hematopoietic stem cell-based forward genetic screens may be valuable for the identification of additional host determinants of malaria pathogenesis.
These results demonstrate for the first time that a JAK-STAT pathway and a MAPK pathway are present down-stream of gp130 in cardiac myocytes and are rapidly activated by LIF both in vitro and in vivo. Activation of gp130 constitutes a novel signaling pathway in cardiac myocytes.
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