Dataset Information

Knock down of Ifitm3 inhibits the adult retinal progenitor cell proliferation

ABSTRACT: Knock down of Ifitm3 inhibits the adult retinal progenitor cell proliferation

PROVIDER: PRJNA736401 | ENA |

REPOSITORIES: ENA

ACCESS DATA

Dataset's files

Source:

			Action	DRS
	SRR14766642_1.fastq.gz	Fastqsanger.gz
	SRR14766642_2.fastq.gz	Fastqsanger.gz
	SRR14766643_1.fastq.gz	Fastqsanger.gz
	SRR14766643_2.fastq.gz	Fastqsanger.gz
	SRR14766644_1.fastq.gz	Fastqsanger.gz

Items per page:

1 - 5 of 12

Similar Datasets

Project description:Ifitm3 (interferon-inducible transmembrane protein 3) was previously identified as an endosomal antiviral effector protein that blocks viral infection1-4. In analyses of gene expression data from patients with B-cell leukemia and lymphoma, we identified Ifitm3 as one of the strongest predictors of poor clinical outcome. In normal resting B-cells, Ifitm3 was minimally expressed and mainly localized in endosomes. However, engagement of the B-cell receptor (BCR) and PI3K-activation strongly induced expression of Ifitm3 and phosphorylation of its N-terminus at Y20, resulting in accumulation at the cell surface. In B-cell leukemia, oncogenic kinases induced phosphorylation at Y20, resulting in constitutive plasma membrane localization of Ifitm3. Ifitm3¯ / ¯ naïve B-cells developed at normal numbers, however, B-cell activation upon antigen encounter, germinal center formation and production of antigen-specific antibodies were compromised. Likewise, oncogenes that typically induce development of leukemia and lymphoma failed to transform Ifitm3¯ / ¯ B-cells. Conversely, a phosphomimetic mutation of Y20 induced oncogenic PI3K-signaling and initiated transformation of premalignant B-cells into overt leukemia. Functional experiments revealed a previously unrecognized function of Ifitm3 as PIP3-scaffold and central amplifier of PI3K signaling downstream of the BCR and adhesion receptors. PI3K signal-amplification depends on binding of Ifitm3 to PIP3 via two lysine residues (K83 and K104) in its conserved intracellular loop. In Ifitm3¯ / ¯ B-cells, lipid rafts were depleted of PIP3, resulting in defective expression of >60 lipid raft-associated surface receptors, which impaired BCR-signaling and cellular adhesion. We conclude that phosphorylation of IFITM3 upon Bcell antigen-encounter induces a dynamic switch from antiviral effector functions in endosomes to a PI3K-amplification loop at the cell surface. IFITM3-dependent amplification of PI3K-signaling downstream of the BCR and adhesion receptors is critical to enable rapid expansion of B-cells with high affinity to antigen. In addition, multiple oncogenes depend on IFITM3 to assemble PIP3- dependent signaling complexes and amplify PI3K-signaling for malignant transformation.

Dataset Information

Knock down of Ifitm3 inhibits the adult retinal progenitor cell proliferation

Dataset's files

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets