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Mindbomb1 is a Novel Negative Regulator of BMP Signaling

ABSTRACT: Mindbomb1 is a Novel Negative Regulator of BMP Signaling.

INSTRUMENT(S): Orbitrap Eclipse

ORGANISM(S): Homo Sapiens (ncbitaxon:9606)

SUBMITTER: Christopher Rose

PROVIDER: MSV000095215 | MassIVE | Tue Jul 02 09:48:00 BST 2024

REPOSITORIES: MassIVE

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Project description:We show that the sensitivity of tsc mutant cells to rapamycin is mediated by TORC1 and can be suppressed by overexpression of the 2-oxoglutarate-Fe(II) dependent oxygenase, Isp7. We show that Isp7 is a novel regulator of amino acids uptake that acts via regulation of gene expression, both upstream and downstream of TOR signaling. suppressed by overexpression of the putative 2-oxoglutarate-Fe(II) dependent oxygenase, Isp7. We show that Isp7 is a novel master regulator of amino acids uptake that acts via regulation of gene expression, both upstream and downstream of TOR signaling. TOR proteins reside in two distinct complexes, TOR complex 1 and 2 (TORC1 and TORC2) that are central for the regulation of cellular growth, proliferation and survival. TOR is also the target for the immunosuppressive and anti-cancer drug rapamycin. In Schizosaccharaomyces pombe, disruption of the TSC complex, mutations in which can lead to the Tuberous Sclerosis syndrome in humans, results in a rapamycin sensitive phenotype under poor nitrogen conditions. We show here that the sensitivity to rapamycin is mediated via inhibition of TORC1 and suppressed by overexpression of isp7+, a member of the family of 2-oxoglutarate-Fe(II) dependent oxygenases. The transcript level of isp7+ is negatively regulated by TORC1 but positively regulated by TORC2. Yet, we find extensive similarity between the transcriptome of cells disrupted for isp7+ and cells mutated in the catalytic subunit of TORC1. Moreover, Isp7 regulates amino acid permease expression similarly to TORC1 and in contrast to TORC2. Overexpression of isp7+ induces TORC1-dependent phosphorylation of ribosomal protein Rps6, while inhibiting TORC2-dependent phosphorylation and activation of the AGC-like kinase Gad8. Taken together, our findings suggest a central role for Isp7 in amino acid homeostasis and the presence of isp7+-dependent regulatory loops that affect both TORC1 and TORC2. 6 Samples (arrays) were performed. We generated pairwise comparison between DISP7 and WT, using Partek Genomics Suite. Genes with pâ¤5%[FDR] and a fold-change difference of â¥2\1.5 or <-2\-1.5 were selected.

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Mindbomb1 is a Novel Negative Regulator of BMP Signaling

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