Volume 20 Issue 4, April 2018

Günter Blobel, recipient of the 1999 Nobel Prize in Physiology or Medicine, died on 18 February 2018 aged 81. He was among the greatest scientists of the twentieth century, whose seminal work on intracellular protein transport and localization revolutionized cell biology.

During mouse back skin development, subsets of fibroblastic lineages transition from anti-fibrotic Engrailed-1 (En1) negative to pro-fibrotic En1-positive cells. Injuries of adult skin heal with scarring, whereas En1-deficient embryonic fibroblasts have the potential to promote scarless regeneration and repair.

The roles of transforming growth factor β (TGF-β) depend on the cellular context. Paraspeckle component 1 now arises as a driver of epithelial-to-mesenchymal transition and stemness transcription factors to redirect effectors from tumour suppressive to pro-metastatic gene promoters, emerging as a contextual determinant of TGF-β function.

The phosphatase PTEN is thought to govern tumour suppression predominantly through PI-3 kinase pathway regulation. A study now shows that a non-catalytic function of CK1α outcompetes the E3 ligase NEDD4-1 to stabilize PTEN, which activates FOXO3A-dependent ATG7 expression and stimulates tumour suppressive autophagy.

A coordinated DNA damage response mediated by p53 to repair DNA lesions or to promote apoptosis is essential for maintenance of genome stability. A study now unveils the long non-coding RNA GUARDIN as a component of this pathway, which protects genome integrity in a pleiotropic fashion.

Mechanical forces influence both cytoplasmic and nuclear events. Kirby and Lammerding discuss recent evidence suggesting that the nucleus itself is a mechanosensor and methods to study nuclear mechanotransduction.

Regulation of pluripotency: Li and Belmonte review the pluripotency gene regulatory network, the molecular principles of pluripotency gene function, regulation by RNA-binding proteins and alternative splicing, heterogeneity and alternative pluripotency states.

Ghose et al. show that EFF-1 fusogen generates a sealed phagosome during engulfment of cells with long processes in Caenorhabditis elegans, and different mechanisms are required for soma, distal and proximal process clearance.

Zhuang et al. demonstrate that suppression of NCoR/SMRT enhances OSKM reprogramming efficiency, and that the barrier mechanism depends on the recruitment of HDAC3 to pluripotency loci by c-MYC.

Gutierrez-Martinez et al. show that an impaired DNA damage response and reduced apoptotic priming in old haematopoietic stem cells (HSCs) contribute to the survival and expansion of damaged HSCs in the bone marrow of aged mice.

Jiang et al. trace two embryonic fibroblast lineages in the mouse, one that does not express engrailed and mediates early dermal development and one that expresses engrailed and mediates scar tissue formation.

Kumar et al. discover a pathway that regulates asymmetric cell cycle entry in budding yeast through Hos3-mediated deacetylation of nucleoporins in daughter cells, which affects the localization of the cell cycle regulators Whi5 and Cln2.

Romero et al. show that the autophagy regulator TP53INP2 represses adipogenesis by promoting GSK3β sequestration and activation of β-catenin through an autophagy-dependent and ESCRT-dependent mechanism.

Nowsheen et al. show that after DNA damage L3MBTL2 is recruited by MDC1 to DNA lesions where it is ubiquitylated by RNF8. Ubiquitylated L3MBTL2 then recruits RNF168 to promote DNA repair.

Cai et al. show that CK1α suppresses lung cancer growth by inducing autophagy through a PTEN–AKT–FOXO3a pathway that ultimately leads to ATG7 expression.

Yeh et al. find that PSPC1 is upregulated in cancer and interacts with Smad2/3 to induce TGF-β1. This leads to increased autocrine TGF-β1 signalling and a switch to pro-metastatic TGF-β1-dependent gene expression.

Hu et al. report that the long non-coding RNA GUARDIN is transcriptionally induced by p53 and promotes genome stability through a dual mechanism to maintain TRF2 expression and BRCA1 stability.