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31.08.16
 
Ubiquitin Family  

Ubiquitin is a small highly conserved protein that is expressed in almost all eukaryotic tissues. These proteins are conjugated onto substrates in a process called ubiquitination. Poly-ubiquitination targets the substrate for destruction by the 26S proteasome. Ubiquitin-signaling is also involved in regulating cell-cell interactions, intracellular targeting and gene expression.

Ubiquitination is catalyzed in a stepwise manner by the three enzymes: First, E1 ubiquitin-activating enzyme catalyzes the ATP-dependent conjugation of a sulfhydryl group to ubiquitin. Then, the ubiquitin is transferred to the sulfhydryl group of E2 ubiquitin-conjugating enzyme. Finally, E3 ubiquitin-protein ligase catalyzes the transfer of ubiquitin from E2 to the target protein. Successive ubiquitin molecules can be linked to lysine 48 of the attached ubiquitin to form poly-ubiquitin chains, amplifying the protein degradation signal.

The rapid turnover of proteins is a critical process for maintaining intracellular homeostasis. Therefore, dysregulated ubiquitination is linked to various diseases such as Creutzfeldt-Jakob disease (CJD) and cervical cancer.

SignalChem offers a divers and comprehensive range of ubiquitin-pathway enzymes, ubiquitin-related proteins and complementary reagents... View list
 
New Active GTPases (including RAS)

There are three human RAS genes encoded in the genome – KRAS, NRAS and HRAS. These genes encode four small GTPases, with each isoform sharing no less than 80% sequence identity with another. Ras GTPases are key activators for several intracellular pathways that promote cell growth and division and inhibit apoptosis. Due to its role in cell proliferation and survival, activated Ras is amongst the most common drivers of oncogenesis.

Aberrant Ras activation occurs due to cell surface receptor overstimulation or through mutations that directly affect GTPase function. In fact, almost a third of all cancers harbor mutations in Ras genes. Most of these mutations cause a defect in the ability to hydrolyze GTP, resulting in a constitutively active GTP-bound enzyme. KRAS is the most prevalent mutated RAS isoform in cancer and KRAS mutants are overrepresented in colorectal and non-small-cell lung carcinomas (NSCLC). NRAS mutations are associated with melanoma, hepatocellular carcinoma, and hematologic malignancies and HRAS mutations are common in kidney, bladder and thyroid carcinomas.

SignalChem has launched Active GTPase enzymes to support drug development research...  View list

 
 

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