The human lung consists of multiple cell types derived from early embryonic compartments. The morphogenesis of the lung, as well as the injury repair of the adult lung, is tightly controlled by a network of signaling pathways with key transcriptional factors. Lung cancer is the third most cancer-related death in the world, which may be developed due to the failure of regulating the signaling pathways. Sox (sex-determining region Y (Sry) box-containing) family transcriptional factors have emerged as potent modulators in embryonic development, stem cells maintenance, tissue homeostasis, and cancerogenesis in multiple processes. Recent studies demonstrated that the members of the Sox gene family played important roles in the development and maintenance of lung and development of lung cancer. In this context, we summarize our current understanding of the role of Sox family transcriptional factors in the morphogenesis of lung, their oncogenic potential in lung cancer, and their potential impact in the diagnosis, prognosis, and targeted therapy of lung cancer.
Previous studies on certain altered holo-isocytochromes c revealed a ؊ -dependent degradation (RDD) phenotype, in which certain altered holo-iso-1-cytochromes c are at normal or nearly normal levels in ؉ strains, but are at low levels or absent in ؊ strains, although wild-type holo-iso-1-cytochrome c is present at normal levels in both ؉ and related ؊ strains. The diminished levels of altered holo-iso-1-cytochrome c are due to the rapid degradation that is carried out by a novel proteolytic pathway in the IMS of mitochondria. SUE1, a nuclear gene that encodes a mitochondrial protein, was identified with a genetic screen for mutants that diminish RDD. The levels of RDD and certain other types of altered holo-iso-1-cytochrome c were elevated in ؊ sue1 strains. Also, ؉ sue1 strains containing certain altered holo-iso-1-cytochromes c grew better on non-fermentable carbon sources than the corresponding ؉ SUE1 strains. These results indicate that Sue1p may play an important role in the degradation of abnormal holo-iso-1-cytochrome c in the mitochondria.Intracellular proteolysis plays an important role in maintaining the integrity of the proper folded state of proteins. It ensures removal of damaged and misfolded polypeptides because they are prone to aggregation. A basic mechanism for control of protein degradation is compartmentalization (1). In eukaryotic cells, proteases have been detected in four compartments: the cytoplasm, nucleus, lysosome, and mitochondrion. The mitochondria have various subcompartments that possess ATP-dependent proteases as a quality control system for selectively removing unassembled or misfolded polypeptides. Several ATP-dependent proteases such as the Pim1 protease in the matrix or AAA (ATPases associated with a variety of cellular activities) proteases in the inner membrane of mitochondria have been identified (2-5).Additional proteolytic pathways may exist in the other two subcompartments of mitochondria: the intermembrane space (IMS) 1 and outer membrane. The existence of an ATP-dependent proteolytic activity in the mitochondrial IMS in mammals has been reported, although the ATP-dependent protease so far has not been identified (6, 7). We report herein a proteolytic pathway in the IMS of mitochondria acting on certain altered holo-iso-1-cytochromes c (holo-1) of the yeast Saccharomyces cerevisiae. S. cerevisiae contains two forms of cytochrome c, iso-1-cytochrome c (iso-1) and iso-2-cytochrome c (iso-2), which are encoded by the nuclear genes CYC1 and CYC7, which normally compose 95 and 5% of total cytochrome c, respectively, in aerobically grown, derepressed cells (8) and which are 80% identical. The isocytochromes c are synthesized in the cytosol as apocytochromes c and subsequently imported into mitochondria. Heme is covalently attached to the apocytochromes c by cytochrome c heme lyase, which is encoded by the gene CYC3, resulting in the formation of the mature holocytochromes c (9). Import of the apocytochromes c is dependent on the action of cytochrome c heme lyase, and cyc3-⌬ m...
The pet20-delta deletion in Saccharomyces cerevisiae causes diminished growth on media containing non-fermentable carbon sources when incubated at both above and below the 30 degrees C optimal growth temperature. Furthermore, the pet20-delta strain has a greatly reduced level of cytochrome c, especially at 37 degrees C. The pet20-delta strain was sensitive to high NaCl and CaCl2 concentrations, hydrogen peroxide, oligomycin, polymixin B, amphotericin B and fluconazole. Biochemical fractionation and immunofluorescence staining demonstrated that Pet20p is located primarily in the mitochondria. Rhodamine B staining of pet20-delta cells showed an altered mitochondrial staining, indicating the possible lack of the mitochondrial membrane potential. We suggest that PET20 encodes a protein required for proper assembly or maintenance of mitochondrial components, but does not serve an enzymatic role. It is also possible that Pet20p may constitute a non-catalytic subunit of an uncharacterized mitochondrial complex or serve as a transporter or a coupling factor.
We report the clinical and laboratory data of 2 patients with different rearrangements involving the short arm of chromosome 18, one with an isochromosome 18p (tetrasomy 18p) and the other with an 18p deletion (monosomy 18p by translocation t(15;18)). Based on molecular cytogenetic findings including high-resolution SNP array, FISH, and multiplex fluorescence PCR, we compared the clinical phenotypes of the 2 patients with other reported patients with 18p deletion, trisomy 18, and isochromosome 18p syndromes to obtain genotype/phenotype correlations. Our findings suggest that a partial monosomy 18p has the better clinical outcome than a tetrasomy 18p.
Background/Aims: Autosomal-dominant polycystic kidney disease (ADPKD) is a heterogeneous genetic disorder caused by mutations in the PKD1 and PKD2 genes. Currently, long-range PCR followed by nested PCR and sequencing (LRNS) is the gold standard approach for PKD1 testing. However, LRNS is complicated by the high structural and sequence complexity of PKD1, which makes the procedure for amplification and analysis of PKD1 difficult. Methods: Here in, we modified the PCR conditions and designed primers for efficient and specific amplification of both the long-range and individual exons of PKD1. Results: Using the modified system, seven long-range fragments were specifically amplified using two distinct sets of conditions, and all individual exon PCR assays were easily performed using a touch-down PCR method. Seven pathogenic or likely pathogenic variants, including two novel truncated frameshift indels and two novel likely pathogenic missense mutations, were identified in eight unrelated patients with or without histories of ADPKD disease (one variant was observed in two unrelated patients). Using combined bioinformatics tools, two indeterminate missense variants were identified in two sporadic patients. Conclusion: Four novel PKD1 variants were identified in this study. We demonstrated that the modified LRNS method achieves high sensitivity and specificity for detecting pathogenic variants of ADPKD.
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