Publications by authors named "Emre Tkacik"
Article Synopsis
- The study addresses the difficulty of understanding how specific sequences in the genome relate to their functions, especially with limited tools for hypermutation.
- A new platform called helicase-assisted continuous editing (HACE) is introduced, which uses CRISPR-Cas9 to induce mutations over large sections of the genome effectively.
- HACE has been applied to study mutations related to drug resistance and missplicing, and it offers a robust way to explore both coding and noncoding genetic variants to better understand their roles in biological functions.
RAF family protein kinases are a key node in the RAS/RAF/MAP kinase pathway, the signaling cascade that controls cellular proliferation, differentiation, and survival in response to engagement of growth factor receptors on the cell surface. Over the past few years, structural and biochemical studies have provided new understanding of RAF autoregulation, RAF activation by RAS and the SHOC2 phosphatase complex, and RAF engagement with HSP90-CDC37 chaperone complexes. These studies have important implications for pharmacologic targeting of the pathway.
View Article and Find Full Text PDFVarious hormones, kinases, and stressors (fasting, heat shock) stimulate 26S proteasome activity. To understand how its capacity to degrade ubiquitylated proteins can increase, we studied mouse ZFAND5, which promotes protein degradation during muscle atrophy. Cryo-electron microscopy showed that ZFAND5 induces large conformational changes in the 19S regulatory particle.
View Article and Find Full Text PDFVarious hormones, kinases, and stressors (fasting, heat shock) stimulate 26S proteasome activity. To understand how its capacity to degrade ubiquitylated protein can increase, we studied ZFAND5, which promotes protein degradation during muscle atrophy. Cryo-electron microscopy showed that ZFAND5 induces large conformational changes in the 19S regulatory particle.
View Article and Find Full Text PDFArticle Synopsis
- - Upon activation by RAS, RAF kinases trigger the MAP kinase cascade to regulate cell growth, with BRAF mutations being particularly common in cancers like malignant melanoma.
- - Current selective BRAF inhibitors are ineffective against cancers fueled by oncogenic RAS or certain BRAF mutations, leading to the development of "type II" RAF inhibitors that target RAF dimers instead.
- - Studies on type II inhibitors tovorafenib and naporafenib show they are most effective against CRAF while being less so against ARAF, revealing their unique binding modes and highlighting potential clinical implications for cancer treatment.
The N-terminally myristoylated matrix (MA) domain of the HIV-1 Gag polyprotein promotes virus assembly by targeting Gag to the inner leaflet of the plasma membrane. Recent studies indicate that, prior to membrane binding, MA associates with cytoplasmic tRNAs (including tRNA), and in vitro studies of tRNA-dependent MA interactions with model membranes have led to proposals that competitive tRNA interactions contribute to membrane discrimination. We have characterized interactions between native, mutant, and unmyristylated (myr-) MA proteins and recombinant tRNA by NMR spectroscopy and isothermal titration calorimetry.
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