Interesting papers, week 8

I realise that week 8 was last week, but I thought I would share the regular paper digest that I send out to people in my lab each week. I love papers and reading about exciting, new science. Sometimes, I also come across publications, even high-impact ones, that are actually flawed in some way or other, and I think it is important to evaluate all new findings critically and highlight potential misinformation.

So join the discussion and add to this list of papers if you have come across something that excited you recently, or perhaps a paper that should be highlighted as problematic!

In future posts, I will try to be more detailed as this is taken straight from an email sent out to the lab!

Transcriptional activation of lipogenesis by insulin requires phosphorylation of MED17 by CK2 (Science Signaling)
Report on how MED17 is phosphorylated by CK2 in response to insulin, but only if it hasn’t been phosphorylated by p38 – something that happens during fasting. MED17 interacts with USF1 in order to be recruited to the FASN promoter. Mechanism demonstrated in liver in vivo and in hepatocytes in vitro. MED17 is a core component of the Mediator complex, by the way. The Mediator complex recruits RNA pol II to active promoters and initiates gene transcription. Lots of biochemical stuff in this paper, too – seems decent.
Pentraxin-3 is a PI3K signaling target that promotes stem cell – like traits in basal-like breast cancers (Science Signaling)
The role of PTX3 appears to be dependent on the particular tumours, but in basal-like breast cancers it seems to enhance PI3K-dependent hyperactivation of key cancer phenotypes. Stem cell-like properties not investigated directly – inferred by observation that PTX3 is highly enriched in mesenchymal / mesenchymal stem cell-like breast cancers.
Gene Essentiality Profiling Reveals Gene Networks and Synthetic Lethal Interactions with Oncogenic Ras (Cell)
It is not directly related to what we do, but good inspiration for what is possible in the future if you want to get a step closer to personalised medicine; i.e. analyse gene essentiality relationship in mutant iPSCs subjected to a CRISPR screen and identify specific liabilities that can guide potential future treatment. Also good discussion on synthetic lethality in cancer and how it may differ for oncogenes compared to mutations in “caretaker” genes.
Two back-to-back Nature papers on GATORs and mTORC1 regulation in relation to nutrient sensing (haven’t read in detail, but seem interesting, and apparently the identified components have been identified in neurological disorders that lead to mTORC1 hyperactivation!): 
KICSTOR recruits GATOR1 to the lysosome and is necessary for nutrients to regulate mTORC1 (Sabatini lab)
SZT2 dictates GATOR control of mTORC1 signalling (Quite impressive with only 3 authors: Min Peng, Na Yin, Ming Li)
The LINK-A lncRNA interacts with PtdIns ( 3 , 4 , 5 ) P 3 to hyperactivate AKT and confer resistance to AKT inhibitors (Lin et al. Nature)
Seems cool, but not read in detail yet as it has A LOT of complex biochemistry so don’t read if your brain is mushy!
Lipid transport by TMEM24 at ER–plasma membrane contacts regulates pulsatile insulin secretion (Lees et al., Science)
Same as above.

A high-throughput, image-based screen to identify kinases involved in brown adipocyte development (Perdikari et al., Science Signaling)

Also not read properly. Using two orthogonal approaches – lentivirus-mediated shRNAs to knockdown kinases (the whole mouse kinome actually!) as well as kinase-specific inhibitors. Apparently, they see that knockdown of the insulin receptor results in improved BAT differentiation!

DNA damage is a major cause of sequencing errors, directly confounding variant identification. (Science)
Seems quite important for the sequencing crew.. Not read beyond abstract, but it suggests that DNA damage during the preparatory stage of DNA for sequencing leads to spurious findings of low-frequency variants, i.e. false-positives. This has implications for the identification of true somatic variants.
Adipose-derived circulating miRNAs regulate gene expression in other tissues (Nature)
I do believe the demonstration that adipose tissue is an important source of miRNAs and that these are likely to regulate other tissues, in an adipose tissue-specific and receptor tissue-specific manner; I will believe the miR-99b story outlined in this paper upon further validation as the stats are not great and n-numbers are low.
Labeling proteins inside living cells using external fluorophores for microscopy. (eLife)
Teng et al. optimise the use of the pore-forming bacterial toxin streptolysin O (SLO) to create small pores in cell membranes in order to facilitate the labelling of intracellular proteins with membrane-impermeant probes, allowing the study of the targeted proteins in live cells. Probes range in size from 2 kDa to 150 kDa; optimised for labelling of cytoplasmic or nuclear proteins, transfected or non-transfected (hence possibly to avoid overexpression artefacts). Cells retain intact membrane structures following recovery. Relevant following our discussion of click chemistry and the issues relating to intracellular labelling of proteins. Also relevant for super resolution imaging applications. Notably, labelling with probes <2 kDa results in background-free labelling because the unbound probe is able to diffuse out through the formed pores during the recovery phase.



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