Multiple functions and dual characteristics of RAB11A in cancers.

Vesicle trafficking is an unceasing and elaborate cellular process that functions in material transport and information delivery. Recent studies have identified the small GTPase, Ras-related protein in brain 11A (RAB11A), as a key regulator in this process. Aberrant RAB11A expression has been reported in several types of cancers, suggesting the important functions and characteristics of RAB11A in cancer. These discoveries are of great significance because therapeutic strategies based on the physiological and pathological status of RAB11A might make cancer treatment more effective, as the molecular mechanisms of cancer development have not been completely revealed. However, these studies on RAB11A have not been reviewed and discussed specifically. Therefore, we summarize and discuss the recent findings of RAB11A involvement in different biological processes, including endocytic recycling regulation, receptors and adhesion molecules recycling, exosome secretion, phagophore formation and cytokinesis, as well as regulatory mechanisms in several tumor types. Moreover, contradictory effects of RAB11A have also been observed in different types of cancers, implying the dual characteristics of RAB11A in cancer, which are either oncogenic or tumor-suppressive. This review on the functions and characteristics of RAB11A highlights the value of RAB11A in inducing multiple important phenotypes based on vesicle trafficking and therefore will offer insights for future studies to reveal the molecular mechanisms, clinical significance, and therapeutic targeting of RAB11A in different cancers.

Targeting USP10 induces degradation of oncogenic ANLN in esophageal squamous cell carcinoma.

Anillin (ANLN) is a mitosis-related protein that promotes contractile ring formation and cytokinesis, but its cell cycle-dependent degradation mechanisms in cancer cells remain unclear. Here, we show that high expression of ANLN promotes cytokinesis and proliferation in esophageal squamous cell carcinoma (ESCC) cells and is associated with poor prognosis in ESCC patients. Furthermore, the findings of the study showed that the deubiquitinating enzyme USP10 interacts with ANLN and positively regulates ANLN protein levels. USP10 removes the K11- and K63-linked ubiquitin chains of ANLN through its deubiquitinase activity and prevents ANLN ubiquitin-mediated degradation. Importantly, USP10 promotes contractile ring assembly at the cytokinetic furrow as well as cytokinesis by stabilizing ANLN. Interestingly, USP10 and the E3 ubiquitin ligase APC/C co-activator Cdh1 formed a functional complex with ANLN in a non-competitive manner to balance ANLN protein levels. In addition, the macrolide compound FW-04-806 (F806), a natural compound with potential for treating ESCC, inhibited the mitosis of ESCC cells by targeting USP10 and promoting ANLN degradation. F806 selectively targeted USP10 and inhibited its catalytic activity but did not affect the binding of Cdh1 to ANLN and alters the balance of the USP10-Cdh1-ANLN complex. Additionally, USP10 expression was positively correlated with ANLN level and poor prognosis of ESCC patients. Overall, targeting the USP10-ANLN axis can effectively inhibit ESCC cell-cycle progression.

Coupling metal and whole-cell catalysis to synthesize chiral alcohols.

BACKGROUND: The combination of metal-catalyzed reactions and enzyme catalysis has been an essential tool for synthesizing chiral pharmaceutical intermediates in the field of drug synthesis. Metal catalysis commonly enables the highly efficient synthesis of molecular scaffolds under harsh organic conditions, whereas enzymes usually catalyze reactions in mild aqueous medium to obtain high selectivity. Since the incompatibility between metal and enzyme catalysis, there are limitations on the compatibility of reaction conditions that must be overcome. FINDINGS: We report a chemoenzymatic cascade reaction involved Palladium (Pd) catalyzed Suzuki-Miyaura coupling and whole-cell catalyzed C = O asymmetric reduction for enantioselective synthesis of value-added chiral alcohol. The cell membrane serves as a natural barrier can protect intracellular enzymes from organic solvents. CONCLUSIONS: With dual advantages of cascade catalysis and biocompatibility, our work provides a rational strategy to harvest chiral alcohols in high yield and excellent enantioselectivity, as a channel to establish chemoenzymatic catalysis.

Molecular epidemiological surveys of H5 subtype highly pathogenic avian influenza viruses in poultry in China during 2007-2009.

To investigate the prevalence and evolution of the H5 subtype highly pathogenic avian influenza (HPAI) viruses circulating in poultry in China during 2007-2009, five molecular epidemiological surveys were carried out. A total of 21, 591 swab samples were collected, and from them 55 H5 HPAI viruses were isolated. None of the 55 viruses carried any known mutations, which can render the virus binding to human SAa2,6Gal receptors. The surveys indicated that live-bird markets, backyard flocks and slaughtering sites were at greater risk of being infected with the viruses during winter, and Clades 2.3.2, 2.3.4 and 7 of the viruses co-circulated in poultry in China during 2007-2009. Viruses within Clades 2.3.2 and 7 have become genetically distinguishable from the viruses isolated before 2007 and antigenically distinguishable from the vaccine strains used in China. Viruses within Clade 2.3.2 have been circulating widely in China and caused a new wave of cross-continental spreading from Asia to Europe.