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Gojanovich, A. D.

Publications and source records attributed to Gojanovich, A. D..

3 recordsLinked to original sources

Differential induction of 14-3-3 paralogs expression during early and late adipogenesis

Obesity is a major public health challenge of the 21st century, particularly in low- and middle-income populations. Adipogenesis plays a central role in the development of obesity and associated metabolic disorders, as it determines adipocyte number, size, and function. The 14-3-3 protein family comprises seven paralogs in mammals that regulate multiple cellular processes, yet their specific roles during adipogenesis remain poorly understood. In this study, we characterized the expression profiles of 14-3-3 paralogs during the early and late stages of adipogenic differentiation using quantitative PCR under standard adipogenic differentiation medium and modified drug-supplemented conditions. We found that the expression of specific paralogs is strongly influenced by the composition of the differentiation medium. The absence of insulin led to an early increase in Ywhaz, which could not be maintained during late adipogenesis and was associated with impaired adipogenic differentiation. In contrast, stimulation with incretins in combination with insulin induced late expression of Ywhag and Ywhab paralogs and promoted the formation of a greater number of smaller lipid droplets. These findings indicate that individual 14-3-3 paralogs exert distinct and context-dependent effects on adipogenesis, highlighting their potential roles as modulators of adipocyte differentiation and metabolic function.

biochemistry↗

An iPSC library from a family with Creutzfeldt-Jakob disease caused by the E200K mutation

The most common subtype of genetic prion disease is caused by the E200K mutation of the prion protein. We have obtained samples from 22 members of a multi-generational Israeli family harboring this mutation, and generated a library of induced pluripotent stem cells (iPSCs) representing nine carriers and four non-carriers. Whole-exome sequencing was performed on all individuals. A comparison of neurons derived from E200K iPSCs to those from non-carriers revealed the presence of several disease-relevant phenotypes. Neurons from E200K carriers were found to contain thioflavin S-positive accumulations of PrP in their cell bodies. In addition, these neurons displayed disruptions of NMDA receptor/PSD95 co-localization at postsynaptic sites. Our study shows that iPSC-derived neurons, which express physiologically relevant levels of mutant PrP in a human neuronal context, can model certain aspects of human prion disease, offering a powerful platform for investigating pathological mechanisms and testing potential therapeutics.

neuroscience↗

14-3-3β paralog is inhibited by acetylation during differentiation to the osteogenic lineage.

14-3-3 protein family binds and regulate hundred of serine/threonine phosphorylated proteins. Considered as redundant, ubiquitous and constantly expressed this protein family was treated as an accessory for many signaling systems. Here we studied the reversible inhibition by acetylation of its essential N-{varepsilon}-lysine 49/51 residue during the osteogenic differentiation of human adipose-derived stem cells (ASC). We found that during the differentiation of ASC the levels of 14-3-3 acK49/51 increase showing that inhibition of 14-3-3 is necessary for this process. Among the 7 paralogs of this family, the inhibition by this posttranslational modification occurs mostly on the paralog {beta} located specifically in the nucleus where 14-3-3 was described to binds to H3 histone and many transcription factors. Short hairpin RNA silencing of 14-3-3{beta} gene but not 14-3-3{gamma} increases significantly the osteogenic potential of the cells. These results show that specifically 14-3-3{beta} is a negative regulator of osteogenesis and its inhibition by acetylation on lysine 51 is the cellular mechanism to regulate it.

cell biology↗