Hunter Lab - Salk Institute
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Recurrent MLK4 Loss-of-Function Mutations Suppress JNK Signaling to Promote Colon Tumorigenesis.

Marusiak, Anna A Stephenson, Natalie L Baik, Hayeon Trotter, Eleanor W Li, Yaoyong Blyth, Karen Mason, Susan Chapman, Phil Puto, Lorena A Read, Jon A ...

Published in Cancer research

MLK4 is a member of the mixed-lineage family of kinases that regulate the JNK, p38, and ERK kinase signaling pathways. MLK4 mutations have been identified in various human cancers, including frequently in colorectal cancer, where their function and pathobiological importance have been uncertain. In this study, we assessed the functional consequence...

How phosphoubiquitin activates Parkin.

Zheng, Xinde Hunter, Tony

Published in Cell research

A recent report, solving the structure of a Parkin-phosphoubiquitin complex, greatly advances the understanding of the Parkin activation mechanism.

Monoclonal 1- and 3-Phosphohistidine Antibodies: New Tools to Study Histidine Phosphorylation.

Fuhs, Stephen Rush Meisenhelder, Jill Aslanian, Aaron Ma, Li Zagorska, Anna Stankova, Magda Binnie, Alan Al-Obeidi, Fahad Mauger, Jacques Lemke, Greg ...

Published in Cell

Histidine phosphorylation (pHis) is well studied in bacteria; however, its role in mammalian signaling remains largely unexplored due to the lack of pHis-specific antibodies and the lability of the phosphoramidate (P-N) bond. Both imidazole nitrogens can be phosphorylated, forming 1-phosphohistidine (1-pHis) or 3-phosphohistidine (3-pHis). We have ...

Discovering the first tyrosine kinase.

Hunter, Tony

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

In the middle of the 20th century, animal tumor viruses were heralded as possible models for understanding human cancer. By the mid-1970s, the molecular basis by which tumor viruses transform cells into a malignant state was beginning to emerge as the first viral genomic sequences were reported and the proteins encoded by their transforming genes w...

Transcriptional Repressor DAXX Promotes Prostate Cancer Tumorigenicity via Suppression of Autophagy.

Puto, Lorena A Brognard, John Hunter, Tony

Published in The Journal of biological chemistry

The DAXX transcriptional repressor was originally associated with apoptotic cell death. However, recent evidence that DAXX represses several tumor suppressor genes, including the DAPK1 and DAPK3 protein kinases, and is up-regulated in many cancers argues that a pro-survival role may predominate in a cancer context. Here, we report that DAXX has pot...

Cancer-associated protein kinase C mutations reveal kinase's role as tumor suppressor.

Antal, Corina E Hudson, Andrew M Kang, Emily Zanca, Ciro Wirth, Christopher Stephenson, Natalie L Trotter, Eleanor W Gallegos, Lisa L Miller, Crispin J Furnari, Frank B ...

Published in Cell

Protein kinase C (PKC) isozymes have remained elusive cancer targets despite the unambiguous tumor promoting function of their potent ligands, phorbol esters, and the prevalence of their mutations. We analyzed 8% of PKC mutations identified in human cancers and found that, surprisingly, most were loss of function and none were activating. Loss-of-f...

Phosphorylation of LC3 by the Hippo kinases STK3/STK4 is essential for autophagy.

Wilkinson, Deepti S Jariwala, Jinel S Anderson, Ericka Mitra, Koyel Meisenhelder, Jill Chang, Jessica T Ideker, Trey Hunter, Tony Nizet, Victor Dillin, Andrew ...

Published in Molecular cell

The protein LC3 is indispensible for the cellular recycling process of autophagy and plays critical roles during cargo recruitment, autophagosome biogenesis, and completion. Here, we report that LC3 is phosphorylated at threonine 50 (Thr(50)) by the mammalian Sterile-20 kinases STK3 and STK4. Loss of phosphorylation at this site blocks autophagy by...

Fitting WWP-1 in the dietary restriction network.

Carrano, Andrea C Hunter, Tony

Published in Cell cycle (Georgetown, Tex.)

A Krüppel-like factor downstream of the E3 ligase WWP-1 mediates dietary-restriction-induced longevity in Caenorhabditis...

Carrano, Andrea C Dillin, Andrew Hunter, Tony

Published in Nature communications

The HECT ubiquitin E3 ligase WWP-1 is a positive regulator of lifespan in response to dietary restriction (DR) in Caenorhabditis elegans. However, substrates of WWP-1 for ubiquitylation in the DR pathway have not yet been identified. Here we identify the C. elegans Krüppel-like factor, KLF-1, as an essential and specific regulator of DR-induced lon...

The genesis of tyrosine phosphorylation.

Hunter, Tony

Published in Cold Spring Harbor perspectives in biology

Tyrosine phosphorylation of proteins was discovered in 1979, but this posttranslational modification had been "invented" by evolution more than a billion years ago in single-celled eukaryotic organisms that were the antecedents of the first multicellular animals. Because sophisticated cell-cell communication is a sine qua non for the existence of m...

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