Suppressor of MEK null (SMEK)/protein phosphatase 4 catalytic subunit (PP4C) is a key regulator of hepatic gluconeogenes...

Published in Proceedings of the National Academy of Sciences of the United States of America

Fasting promotes hepatic gluconeogenesis to maintain glucose homeostasis. The cAMP-response element binding protein (CREB)-regulated transcriptional coactivator 2 (CRTC2) is responsible for transcriptional activation of gluconeogenic genes and is critical for conveying the opposing hormonal signals of glucagon and insulin in the liver. Here, we sho...

Regulation of the Chlamydomonas cell cycle by a stable, chromatin-associated retinoblastoma tumor suppressor complex.

Published in The Plant cell

We examined the cell cycle dynamics of the retinoblastoma (RB) protein complex in the unicellular alga Chlamydomonas reinhardtii that has single homologs for each subunit-RB, E2F, and DP. We found that Chlamydomonas RB (encoded by MAT3) is a cell cycle-regulated phosphoprotein, that E2F1-DP1 can bind to a consensus E2F site, and that all three prot...

RING domain dimerization is essential for RNF4 function.

Published in The Biochemical journal

RNF4 [RING (really interesting new gene) finger protein 4] family ubiquitin ligases are RING E3 ligases that regulate the homoeostasis of SUMOylated proteins by promoting their ubiquitylation. In the present paper we report that the RING domain of RNF4 forms a stable dimer, and that dimerization is required for ubiquitin transfer. Our results sugge...

Genetic and cellular mechanisms of oncogenesis: Editorial overview

Published in Current Opinion in Genetics & Development

Regulation of the cell cycle by a stable, chromatin-associated retinoblastoma tumor suppressor complex

Published in Plant and Cell Physiology

CtIP links DNA double-strand break sensing to resection.

Published in Molecular cell

In response to DNA double-strand breaks (DSBs), cells sense the DNA lesions and then activate the protein kinase ATM. Subsequent DSB resection produces RPA-coated ssDNA that is essential for activation of the DNA damage checkpoint and DNA repair by homologous recombination (HR). However, the biochemical mechanism underlying the transition from DSB ...

The F box protein Fbx6 regulates Chk1 stability and cellular sensitivity to replication stress.

Published in Molecular Cell

ATR and Chk1 are two key protein kinases in the replication checkpoint. Activation of ATR-Chk1 has been extensively investigated, but checkpoint termination and replication fork restart are less well understood. Here, we report that DNA damage not only activates Chk1, but also exposes a degron-like region at the carboxyl terminus of Chk1 to an Fbx6...

A conserved ubiquitination pathway determines longevity in response to diet restriction.

Published in Nature

Dietary restriction extends longevity in diverse species, suggesting that there is a conserved mechanism for nutrient regulation and prosurvival responses. Here we show a role for the HECT (homologous to E6AP carboxy terminus) E3 ubiquitin ligase WWP-1 as a positive regulator of lifespan in Caenorhabditis elegans in response to dietary restriction....

Tyrosine phosphorylation: thirty years and counting.

Published in Current Opinion in Cell Biology

In the 30 years since its discovery, tyrosine phosphorylation has emerged as a fundamentally important mechanism of signal transduction and regulation in all eukaryotic cells, governing many processes, including cell proliferation, cell cycle progression, metabolic homeostasis, transcriptional activation, neural transmission, differentiation and de...