Explore the vast range of titles available.

The protein prenylation is one of the essential post-translational protein modifications, which extensively exists in the eukaryocyte. It includes protein farnesylation and geranylgeranylation, using farnesyl pyrophosphate （FPP） or geranylgeranyl pyrophosphate （GGPP） as the substrate, respectively. The prenylation occurs by covalent addition of these two types of isoprenoids to cysteine residues at or near the carboxyl terminus of the proteins that possess CaaX motif, such as Ras small GTPase family. The attachment of hydrophobic prenyl groups can anchor the proteins to intracellular membranes and trigger downstream cell signaling pathway. Geranylgeranyl biphosphate synthase （GGPPS） catalyzes the synthesis of 20-carbon GGPP from 15-carbon FPP. The abnormal expression of this enzyme will affect the relative content of FPP and GGPP, and thus disrupts the balance between protein farnesylation and geranylgeranylation, which participates into various aspects of cellular physiology and pathology. In this paper, we mainly review the property of this important protein post-translational modification and research progress in its regulation of cigarette smoke induced pulmonary disease, adipocyte insulin sensitivity, the inflammation response of Sertoli cells, the hepatic lipogenesis and the cardiac hypertrophy.

RAG1 and RAG2 proteins are key components in V（D）J recombination. The core region of RAG1 is capable of catalyzing the recombination reaction; however, the biological function of non-core RAG1 remains largely unknown. Here, we show that in a murine-model carrying the RAG1 ring-finger conserved cysteine residue mutation （C325Y）, V（D）J recombination was abrogated at the cleavage step, and this effect was accompanied by decreased mono-ubiquitylation of histone H3. Further analyses suggest that un-ubiquitylated histone H3 restrains RAG1 to the chromatin by interacting with the N-terminal 218 amino acids of RAG1. Our data provide evidence for a model in which ubiquitylation of histone H3 mediated by the ring-finger domain of RAG1 triggers the release of RAG1, thus allowing its transition into the cleavage phase. Collectively, our findings reveal that the non-core region of RAG1 facilitates chromosomal V（D）J recombination in a ubiquitylation-dependent pathway.

The atypical PKC isoforms （ζ and t） play essential roles in regulating various cellular processes. Both the hetero-interaction between PKCζand p62 through their N-terminal PB 1 domains and the homo-oligomerization of p62 via its PB 1 domain are critical for the activation of NF-r.B signaling; however, the molecular mechanisms concerning the formation and regulation of these homotypic complexes remain unclear. Here we determined the crystal structure of PKCζ-PB 1 in complex with a mono- meric p62-PB 1 mutant, where the massive electrostatic interactions between the acidic OPCA motif of PKCζ-PB 1 and the basic surface of p62-PB 1, as well as additional hydrogen bonds, ensure the formation of a stable and specific complex. The PKCζ-p62 interaction is interfered with the modification of a specific Cys of PKCζ by the antiarthritis drug aurothiomalate, though all four cysteine residues in the PKCζ-PB 1 domain can be modified in in vitro assay. In addition, detailed structural and biochemical analyses demonstrate that the PB 1 domains of aPKCs belong to the type I group, which can depolymerize the high-molecular-weight p62 aggregates into homo-oligomers of lower order. These data together unravel the molecular mecha- nisms of the homo- or hetero-interactions between p62 and PKCζ and provide the basis for designing inhibitors of NF-r,.B sig- naling.