The function of the three phosphoribosyl pyrophosphate synthetase (Prs) genes in hyphal growth and conidiation in Aspergillus nidulans.

Phosphoribosyl pyrophosphate synthetase, which is encoded by the Prs gene, catalyses the reaction of ribose-5-phosphate and adenine ribonucleotide triphosphate (ATP) and has central importance in cellular metabolism. However, knowledge about how Prs family members function and contribute to total 5-phosphoribosyl-α-1-pyrophosphate (PRPP) synthetase activity is limited. In this study, we identified that the filamentous fungus Aspergillus nidulans genome contains three PRPP synthase-homologous genes (AnprsA, AnprsB and AnprsC), among which AnprsB and AnprsC but not AnprsA are auxotrophic genes. Transcriptional expression profiles revealed that the mRNA levels of AnprsA, AnprsB and AnprsC are dynamic during germination, hyphal growth and sporulation and that they all showed abundant expression during the vigorous hyphal growth time point. Inhibiting the expression of AnprsB or AnprsC in conditional strains produced more effects on the total PRPP synthetase activity than did inhibiting AnprsA, thus indicating that different AnPrs proteins are unequal in their contributions to Prs enzyme activity. In addition, the constitutive overexpression of AnprsA or AnprsC could significantly rescue the defective phenotype of the AnprsB-absent strain, suggesting that the function of AnprsB is not a specific consequence of this auxotrophic gene but instead comes from the contribution of Prs proteins to PRPP synthetase activity.

Protein phosphatase 2A (PP2A) regulatory subunits ParA and PabA orchestrate septation and conidiation and are essential for PP2A activity in Aspergillus nidulans.

Protein phosphatase 2A (PP2A) is a major intracellular protein phosphatase that regulates multiple aspects of cell growth and metabolism. Different activities of PP2A and subcellular localization are determined by its regulatory subunits. Here we identified and characterized the functions of two protein phosphatase regulatory subunit homologs, ParA and PabA, in Aspergillus nidulans. Our results demonstrate that ParA localizes to the septum site and that deletion of parA causes hyperseptation, while overexpression of parA abolishes septum formation; this suggests that ParA may function as a negative regulator of septation. In comparison, PabA displays a clear colocalization pattern with 4',6-diamidino-2-phenylindole (DAPI)-stained nuclei, and deletion of pabA induces a remarkable delayed-septation phenotype. Both parA and pabA are required for hyphal growth, conidiation, and self-fertilization, likely to maintain normal levels of PP2A activity. Most interestingly, parA deletion is capable of suppressing septation defects in pabA mutants, suggesting that ParA counteracts PabA during the septation process. In contrast, double mutants of parA and pabA led to synthetic defects in colony growth, indicating that ParA functions synthetically with PabA during hyphal growth. Moreover, unlike the case for PP2A-Par1 and PP2A-Pab1 in yeast (which are negative regulators that inactivate the septation initiation network [SIN]), loss of ParA or PabA fails to suppress defects of temperature-sensitive mutants of the SEPH kinase of the SIN. Thus, our findings support the previously unrealized evidence that the B-family subunits of PP2A have comprehensive functions as partners of heterotrimeric enzyme complexes of PP2A, both spatially and temporally, in A. nidulans.

Clinical value of combined detection of LDH, TPS, CEA and beta2-MG in patients with non- Hodgkin's lymphoma / 南方医科大学学报

<p><b>OBJECTIVE</b>To study the clinical value of combined detection of 4 tumor markers, namely lactic dehydrogenate (LDH), tissue polypeptide specific antigen (TPS), carcinoembryonic antigen (CEA) and beta2-microglobulin (beta2-MG) in patients with non-Hodgkin's lymphoma (NHL).</p><p><b>METHODS</b>The serum level of LDH was determined with automatic biochemical analyzer and TPS, CEA and beta2-MG levels were determined by enzyme-linked immumosorbent assay (ELISA) in 59 patients with NHL and 40 healthy adults.</p><p><b>RESULTS</b>The levels of the 4 tumor markers were significantly higher in NHL patients than in the healthy control subjects (P<0.05). After chemotherapy, the serum levels of TPS and beta2-MG were significantly lowered in the patients who showed favorable response to the treatment (P<0.05), but the levels of LDH and CEA showed no significant change (P>0.05). The serum levels of LDH, TPS, CEA and beta2-MG in the patients in a stable or progressive phase did had no significant changes after chemotherapy (P>0.05).</p><p><b>CONCLUSION</b>Combined detection of LDH, TPS, CEA and beta2-MG can be helpful to assist diagnosis of NHL and treatment evaluation.</p>