The transcription factor ZNF224 is a Kruppel-like zinc finger protein that consists of 707 amino acids and contains 19 tandemly repeated C2H2 zinc finger domains that mediate DNA binding and protein–protein interactions. ZNF224 was originally identified as a transcriptional repressor of genes involved in energy metabolism, and it was demonstrated that ZNF224-mediated transcriptional repression needs the interaction of its KRAB repressor domain with the co-repressor KAP1 and its zinc finger domains 1–3 with the arginine methyltransferase PRMT5. Furthermore, the protein ZNF255 was identified as an alternative isoform of ZNF224 that possesses different domain compositions mediating distinctive functional interactions. Subsequent studies showed that ZNF224 is a multifunctional protein able to exert different transcriptional activities depending on the cell context and the variety of its molecular partners. Indeed, it has been shown that ZNF224 can act as a repressor, an activator and a cofactor for other DNA-binding transcription factors in different human cancers. Here, we provide a brief overview of the current knowledge on the multifaceted interactions of ZNF224 and the resulting different roles of this protein in various cellular contexts.

Enzymes purified from psychrophilic microorganisms prove to be efficient catalysts at low temperatures and possess a great potential for biotechnological applications. The low-temperature catalytic activity has to come from specific structural fluctuations involving the active site region, however, the relationship between protein conformational stability and enzymatic activity is subtle. We provide a survey of the thermodynamic stability of globular proteins and their rationalization grounded in a theoretical approach devised by one of us. Furthermore, we provide a link between marginal conformational stability and protein flexibility grounded in the harmonic approximation of the vibrational degrees of freedom, emphasizing the occurrence of long-wavelength and excited vibrations in all globular proteins. Finally, we offer a close view of three enzymes: chloride-dependent α-amylase, citrate synthase, and β-galactosidase.

Background: Obesity and type 2 diabetes mellitus, which are widespread throughout the world, require therapeutic interventions targeted to solve clinical problems (insulin resistance, hyperglycaemia, dyslipidaemia and steatosis). Several natural compounds are now part of the therapeutic repertoire developed to better manage these pathological conditions. Cladosporols, secondary metabolites from the fungus Cladosporium tenuissimum, have been characterised for their ability to control cell proliferation in human colon cancer cell lines through peroxisome proliferator-activated receptor gamma (PPARγ)-mediated modulation of gene expression. Here, we report data concerning the ability of cladosporols to regulate the differentiation of murine 3T3-L1 preadipocytes. Methods: Cell counting and MTT assay were used for analysing cell proliferation. RT-PCR and Western blotting assays were performed to evaluate differentiation marker expression. Cell migration was analysed by woundhealing assay. Results: We showed that cladosporol A and B inhibited the storage of lipids in 3T3-L1 mature adipocytes, while their administration did not affect the proliferative ability of preadipocytes. Moreover, both cladosporols downregulated mRNA and protein levels of early (C/EBPα and PPARγ) and late (aP2, LPL, FASN, GLUT-4, adiponectin and leptin) differentiation markers of adipogenesis. Finally, we found that proliferation and migration of HT-29 colorectal cancer cells were inhibited by conditioned medium from cladosporol-treated 3T3-L1 cells compared with the preadipocyte conditioned medium. Conclusions: To our knowledge, this is the first report describing that cladosporols inhibit in vitro adipogenesis and through this inhibition may interfere with HT-29 cancer cell growth and migration. General significance: Cladosporols are promising tools to inhibit concomitantly adipogenesis and control colon cancer initiation and progression. IntroductionObesity is a risk factor for several diseases such as type 2 diabetes, metabolic syndrome, hypertension, hyperlipidaemia, atherosclerosis and cancer. Hyperplasia (an increase in adipocyte numbers) and hypertrophy (an increase in adipocyte mass) both lead to obesity [1]. Genetics, metabolism, nutritional status, exercise and, in general, habits of life may differentially contribute to the development of obesity.

The amount of water-accessible-surface-area, WASA, buried upon protein–protein association is a good measure of the non-covalent complex stability in water; however, the dependence of the binding Gibbs free energy change upon buried WASA proves to be not trivial. We assign a precise physicochemical role to buried WASA in the thermodynamics of non-covalent association and perform close scrutiny of the contributions favoring and those contrasting protein–protein association. The analysis indicates that the decrease in solvent-excluded volume, an entropic effect, described by means of buried WASA, is the molecular driving force of non-covalent association in water.