The F box protein Fbx6 regulates Chk1 stability and cellular sensitivity to replication stress.
Yw, Zhang J, Brognard C, Coughlin Z, You M, Dolled-Filhart A, Aslanian G, Manning Rt, Abraham T, Hunter
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.
Ac, Carrano Z, Liu A, Dillin T, Hunter
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....
PI-3 kinase activity is necessary for ERK1/2-induced disruption of mammary epithelial architecture
Pearson, Gray W Hunter, Tony
Published in Breast Cancer Research
IntroductionEpithelial tumors, including breast cancer, are being identified and treated at earlier stages of tumor development because of technological advances in screening and detection methods. It is likely that early-stage epithelial tumors, such as mammary ductal carcinoma in situ (DCIS), will be amenable to new and more efficacious diagnosti...
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...
TORC-specific phosphorylation of mammalian target of rapamycin (mTOR): phospho-Ser2481 is a marker for intact mTOR signa...
J, Copp G, Manning T, Hunter
Published in Cancer Research
The mammalian target of rapamycin (mTOR) serine/threonine kinase is the catalytic component of two evolutionarily conserved signaling complexes. mTOR signaling complex 1 (mTORC1) is a key regulator of growth factor and nutrient signaling. S6 kinase is the best-characterized downstream effector of mTORC1. mTOR signaling complex 2 (mTORC2) has a role...
Genic regions of a large salamander genome contain long introns and novel genes
Smith, Jeramiah J Putta, Srikrishna Zhu, Wei Pao, Gerald M Verma, Inder M Hunter, Tony Bryant, Susan V Gardiner, David M Harkins, Timothy T Voss, S Randal ...
Published in BMC Genomics
BackgroundThe basis of genome size variation remains an outstanding question because DNA sequence data are lacking for organisms with large genomes. Sixteen BAC clones from the Mexican axolotl (Ambystoma mexicanum: c-value = 32 × 109 bp) were isolated and sequenced to characterize the structure of genic regions.ResultsAnnotation of genes within BAC...
Microarray and cDNA sequence analysis of transcription during nerve-dependent limb regeneration
Monaghan, James R Epp, Leonard G Putta, Srikrishna Page, Robert B Walker, John A Beachy, Chris K Zhu, Wei Pao, Gerald M Verma, Inder M Hunter, Tony ...
Published in BMC Biology
Background Microarray analysis and 454 cDNA sequencing were used to investigate a centuries-old problem in regenerative biology: the basis of nerve-dependent limb regeneration in salamanders. Innervated (NR) and denervated (DL) forelimbs of Mexican axolotls were amputated and transcripts were sampled after 0, 5, and 14 days of regeneration.Results ...
RING finger proteins as E3 ubiquitin ligases
Joazeiro, C A P Tony Hunter
CtIP links DNA double-strand break sensing and resection
You, Z Shi, L Z Zhu, Q Wu, P Zhang, Y W Basilio, A Tonnu, N Verma, I M Berns, M W Tony Hunter ...
Published in Molecular and Cellular Therapies
Degradation of activated protein kinases by ubiquitination.
Z, Lu T, Hunter
Published in Annual Review of Biochemistry
Protein kinases are important regulators of intracellular signal transduction pathways and play critical roles in diverse cellular functions. Once a protein kinase is activated, its activity is subsequently downregulated through a variety of mechanisms. Accumulating evidence indicates that the activation of protein kinases commonly initiates their ...