Caspase-mediated proteolysis is a critical and central element of the apoptotic process, and caspase 3, one of the effector caspases, is proposed to play essential roles in the nuclear morphological changes of apoptotic cells. Although many substrates for caspase 3 localize in the nucleus and caspase 3 translocates from the cytoplasm to the nuclei ...
c-Jun, a major transcription factor in the activating protein 1 family of regulatory proteins, is activated by many physiologic and pathological stimuli. We show here that c-Jun was downregulated in response to osmotic stress via ubiquitination-dependent degradation by the PHD/RING finger domain of MEKK1, which exhibited E3 ubiquitin ligase activit...
With basic and pharmaceutical researchers, chemists, pharmacologists, and clinicians, the Targeting the Kinome meeting brought together a tremendous group of scientists to discuss the past, present, and future of protein kinase research, with a special emphasis on cancer therapy development. The topics ranged from the kinases themselves as drug tar...
The F-actin cytoskeleton is a fundamental component of all eukaryotic cells. It provides force and stability and plays an integral role in a diverse array of cellular processes. The spatiotemporal regulation of F-actin dynamics is essential for proper biological output. The basic molecular machinery underlying the assembly and disassembly of filame...
The mammalian focal adhesion kinase (FAK) family of non-receptor protein-tyrosine kinases has been implicated in controlling a multitude of cellular responses to the engagement of cell-surface integrins and G-protein-coupled receptors. The high level of sequence conservation between the mammalian proteins and the Drosophila homologue of FAK, Fak56,...
ERK1/2 MAP kinases are important regulators in cellular signaling, whose activity is normally reversibly regulated by threonine-tyrosine phosphorylation. In contrast, we have found that stress-induced ERK1/2 activity is downregulated by ubiquitin/proteasome-mediated degradation of ERK1/2. The PHD domain of MEKK1, a RING finger-like structure, exhib...
Tumor-specific pyruvate kinase M2 (PKM2) is essential for the Warburg effect. In addition to its well-established role in aerobic glycolysis, PKM2 directly regulates gene transcription. However, the mechanism underlying this nonmetabolic function of PKM2 remains elusive. We show here that PKM2 directly binds to histone H3 and phosphorylates histone...
Tyrosine phosphorylation is catalyzed by protein tyrosine kinases, which are represented by 90 genes in the human genome. Here, we present the set of 107 genes in the human genome that encode members of the four protein tyrosine phosphatase (PTP) families. The four families of PTPases, their substrates, structure, function, regulation, and the role...
Post-translational modification by SUMO is a highly conserved pathway in eukaryotes that plays very important regulatory roles in many cellular processes. Deregulation of the SUMO pathway contributes to the development and progression of many diseases including cancer. Therefore, identifying additional SUMO substrates and studying how their cellula...
The TSC1-TSC2 tumor suppressor complex serves as an interface between insulin and nutrient signaling pathways and the cell growth machinery. Recent work has indicated that the TSC1-TSC2 complex plays a role in the pathobiology of a number of tumor predisposition syndromes, including tuberous sclerosis (TSC1/2), Peutz-Jeghers syndrome (LKB1), and Co...
