EGFR inhibitor suppresses tumor growth by blocking lipid uptake and cholesterol synthesis in non-small cell lung cancer.

Accelerated cholesterol and lipid metabolism are hallmarks of non-small cell lung cancer (NSCLC). Recently, epidermal growth factor receptor (EGFR) signaling has been shown to regulate de novo cholesterol synthesis and low-density lipoprotein receptor (LDLR) expression through SREBP-1-dependent pathways. This suggests that targeting EGFR signaling in cholesterol metabolism might provide a new therapeutic strategy for NSCLC.

Tho2-mediated escort of Nrd1 regulates the expression of aging-related genes.

The relationship between aging and RNA biogenesis and trafficking is attracting growing interest, yet the precise mechanisms are unknown. The THO complex is crucial for mRNA cotranscriptional maturation and export. Herein, we report that the THO complex is closely linked to the regulation of lifespan.

Sus1 maintains a normal lifespan through regulation of TREX-2 complex-mediated mRNA export.

Eukaryotic gene expression requires multiple cellular events, including transcription and RNA processing and transport. Sus1, a common subunit in both the Spt-Ada-Gcn5 acetyltransferase (SAGA) and transcription and export complex-2 (TREX-2) complexes, is a key factor in coupling transcription activation to mRNA nuclear export. Here, we report that the SAGA DUB module and TREX-2 distinctly regulate yeast replicative lifespan in a Sir2-dependent and -independent manner, respectively.

Ubiquitin-Specific Protease 29 Regulates Cdc25A-Mediated Tumorigenesis.

Cell division cycle 25A (Cdc25A) is a dual-specificity phosphatase that is overexpressed in several cancer cells and promotes tumorigenesis. In normal cells, Cdc25A expression is regulated tightly, but the changes in expression patterns in cancer cells that lead to tumorigenesis are unknown. In this study, we showed that ubiquitin-specific protease 29 (USP29) stabilized Cdc25A protein expression in cancer cell lines by protecting it from ubiquitin-mediated proteasomal degradation.

Ubiquitin-Specific Protease 3 Deubiquitinates and Stabilizes Oct4 Protein in Human Embryonic Stem Cells.

Oct4 is an important mammalian POU family transcription factor expressed by early human embryonic stem cells (hESCs). The precise level of Oct4 governs the pluripotency and fate determination of hESCs. Several post-translational modifications (PTMs) of Oct4 including phosphorylation, ubiquitination, and SUMOylation have been reported to regulate its critical functions in hESCs.

E3 Ubiquitin Ligase APC/C Regulation of Phenylalanine Hydroxylase Stability and Function.

Phenylketonuria (PKU) is an autosomal recessive metabolic disorder caused by the dysfunction of the enzyme phenylalanine hydroxylase (PAH). Alterations in the level of PAH leads to the toxic accumulation of phenylalanine in the blood and brain. Protein degradation mediated by ubiquitination is a principal cellular process for maintaining protein homeostasis.

Maintenance of hPSCs under Xeno-Free and Chemically Defined Culture Conditions.

Previously, the majority of human embryonic stem cells and human induced pluripotent stem cells have been derived on feeder layers and chemically undefined medium. Those media components related to feeder cells, or animal products, often greatly affect the consistency of the cell culture. There are clear advantages of a defined, xeno-free, and feeder-free culture system for human pluripotent stem cells (hPSCs) cultures, since consistency in the formulations prevents lot-to-lot variability.

Loss of the Set2 histone methyltransferase increases cellular lifespan in yeast cells.

The post-translational modification of histones has been implicated in the regulation of cellular lifespan. Previously, we reported that cellular aging is associated with increased ubiquitylation of histone H2B and methylation of histone H3 at lysines 4 and 79 in yeast telomeric heterochromatin. Here, we show the antagonistic role of Set2 methyltransferase, which is specific for histone H3 at lysine 36, in regulating telomeric silencing and cellular lifespan.

The RNA polymerase II Rpb4/7 subcomplex regulates cellular lifespan through an mRNA decay process.

In budding yeast, a highly conserved heterodimeric protein complex that is composed of the Rpb4 and Rpb7 proteins within RNA polymerase II shuttles between the nucleus and cytoplasm where it coordinates various steps of gene expression by associating with mRNAs. Although distinct stages of gene expression potentially contribute to the regulation of cellular lifespan, little is known about the underlying mechanisms. Here, we addressed the role of the dissociable Rpb4/7 heterodimeric protein complex in the regulation of replicative lifespan during various stages of gene expression in the yeast Saccharomyces cerevisiae.

Cellular aging is associated with increased ubiquitylation of histone H2B in yeast telomeric heterochromatin.

Epigenetic changes in chromatin state are associated with aging. Notably, two histone modifications have recently been implicated in lifespan regulation, namely acetylation at H4 lysine 16 in yeast and methylation at H3 lysine 4 (H3K4) in nematodes. However, less is known about other histone modifications.