Publications by authors named "S Earnest"
The transcription factor achaete-scute complexhomolog 1 (ASCL1) is a lineage oncogene that is central in growth and survival of the majority of small cell lung cancers and neuroendocrine (NE) non-small cell lung cancers (NSCLC) that express it. Targeting ASCL1, or its downstream pathways, remains a challenge. Small cell lung cancers and NSCLC-NE that express ASCL1 exhibit relatively low ERK1/2 activity, in dramatic contrast to NSCLCs in which the ERK pathway plays a major role in pathogenesis.
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- The study investigates the WNK-OSR1/SPAK protein kinase signaling pathway, which is known to regulate ion homeostasis and cell volume, to discover its other potential signaling roles.
- Researchers analyzed the binding specificity of the conserved C-terminal (CCT) domains of OSR1 and SPAK to identify possible interaction motifs in human proteins, highlighting key consensus sequences and ranking about 3,700 identified motifs.
- The findings reveal not only that a significant portion of previously known motifs align with predicted ones but also introduce new variants lacking a previously essential arginine, showing an expanded functionality of CCT domains in linking WNK signaling to various cellular functions.
Article Synopsis
- - Activity-regulated cytoskeleton-associated protein (Arc) is crucial for various types of synaptic plasticity, such as long-term potentiation and depression, and can also form virus-like particles to facilitate mRNA transport between cells.
- - Arc undergoes several post-translational modifications, particularly phosphorylation by protein kinase C (PKC), which occurs on specific serine residues, affecting its function.
- - Mutating these serines to mimic phosphorylation leads to reduced palmitoylation, impaired nucleic acid binding, and instability of Arc oligomers, suggesting that PKC phosphorylation may restrict synaptic weakening and mRNA transport.
The conserved p38 MAPK family is activated by phosphorylation during stress responses and inactivated by phosphatases. C. elegans PMK-1 p38 MAPK initiates innate immune responses and blocks development when hyperactivated.
View Article and Find Full Text PDFThe transcription factor achaete-scute complex homolog 1 (ASCL1) is a lineage oncogene that is central for the growth and survival of small cell lung cancers (SCLC) and neuroendocrine non-small cell lung cancers (NSCLC-NE) that express it. Targeting ASCL1, or its downstream pathways, remains a challenge. However, a potential clue to overcoming this challenage has been information that SCLC and NSCLC-NE that express ASCL1 exhibit extremely low ERK1/2 activity, and efforts to increase ERK1/2 activity lead to inhibition of SCLC growth and surival.
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