Longevity Assurance 5 (LASS5), a member of the LASS/Ceramide Synthases family, synthesizes C16-ceramide and is implicated in tumor biology. However, its precise role is not yet well understood. A yeast two-hybrid screen was performed using a human cDNA library to identify potential LASS5-interaction partners. One identified clone encodes succinate dehydrogenase subunit B (SDHB). Mammalian two-hybrid assays showed that LASS5 interacts with SDHB, and the result was also confirmed by GST pull-down and co-immunoprecipitation assays. The C-terminal fragment of SDHB was required for the interaction. LASS5 and SDHB were co-localized in COS-7 cells. LASS5 and SDHB expressions were found to be up-regulated in neuroglioma tissue. Transfection assays showed that LASS5 or SDHB expression repressed p53 or p21 reporter activity, respectively. Simultaneous LASS5 and SDHB expression resulted in stronger repression of p53 and p21 reporter activity, suggesting that LASS5 and SDHB interaction may synergistically affect transcriptional regulation of p53 and p21. Our data provide new molecular insights into potential roles of LASS5 and SDHB in tumor biology.

The human Hole gene (hHole) encodes a six-transmembrane protein with 319- amino acids. Our previous study showed that hHole was strongly expressed in adult heart and may act as a suppressor of extracellular signal-regulated kinases (ERKs), overactivation of which contributed to pathological cardiac hypertrophy. In this study, it was observed that Hole expression was up-regulated in murine hypertrophic hearts. In a cardiac specific transgenic mouse model, it was observed that overexpression of hHole specifically in heart attenuated cardiac hypertrophy and fibrosis induced by isoproterenol (ISO), with blunted transcriptions of ERK1/2, total ERK1/2 proteins and phosphorylated ERK1/2 (p-ERK1/2) levels. Furthermore, overexpression of hHole in mice by hydrodynamic tail-vein injection with hHole plamids also inhibited cardiac hypertrophy induced by ISO. Our work identified hHole as a novel repressor of cardiac hypertrophy, and provided new insights into the possible target for the prevention or treatment of cardiac diseases.

Background: Four-and-a-half LIM domains protein 1 (FHL1) mutations are associated with human myopathies. However, the function of this protein in skeletal development remains unclear.Methods: Whole-mount in situ hybridization and embryo immunostaining were performed.Results: Zebrafish Fhl1A is the homologue of human FHL1. We showed that fhl1A knockdown causes defective skeletal muscle development, while injection with fhl1A mRNA largely recovered the muscle development in these fhl1A morphants. We also demonstrated that fhl1A knockdown decreases the number of satellite cells. This decrease in satellite cells and the emergence of skeletal muscle abnormalities were associated with alterations in the gene expression of myoD, pax7, mef2ca and skMLCK. We also demonstrated that fhl1A expression and retinoic acid (RA) signalling caused similar skeletal muscle development phenotypes. Moreover, when treated with exogenous RA, endogenous fhl1A expression in skeletal muscles was robust. When treated with DEAB, an RA signalling inhibitor which inhibits the activity of retinaldehyde dehydrogenase, fhl1A was downregulated.Conclusion: fhl1A functions as an activator in regulating the number of satellite cells and in skeletal muscle development. The role of fhl1A in skeletal myogenesis is regulated by RA signaling.