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S Nishimori

Publications and source records attributed to S Nishimori.

12 recordsLinked to original sources

Smad-mediated transcription is required for transforming growth factor-beta 1-induced p57(Kip2) proteolysis in osteoblastic cells.

Cyclin-dependent kinase inhibitory proteins (CKIs) are negative regulators of the cell cycle. Of all CKIs, only p57(Kip2) plays an essential role(s) that other CKIs cannot compensate for in embryonic development. Recently, we found that p57(Kip2) is degraded through the ubiquitin-proteasome pathway in osteoblastic cells stimulated to proliferation by transforming growth factor (TGF)-beta1 (Urano, T., Yashiroda, H., Muraoka, M., Tanaka, K., Hosoi, T., Inoue, S., Ouchi, Y., and Toyoshima, H. (1999) J. Biol. Chem. 274, 12197-12200). We report here that TGF-beta1-induced p57(Kip2) proteolysis is mediated through transcription by the Smad pathway. When the constitutively active form of the TGF-beta type I receptor ALK-5(TD) was ectopically expressed in osteoblastic cells, p57(Kip2) that had been accumulated by serum starvation causing the cell-cycle arrest was rapidly degraded in a manner analogous to TGF-beta1 stimulation. Moreover, Smad2 or Smad3 with Smad4 enhanced the proteolytic pathway of p57(Kip2). The degradation of p57(Kip2) evoked by TGF-beta1 was blocked by forced expression of an inhibitory Smad called Smad7 or by the addition of actinomycin D or alpha-amanitin. These results indicate that accelerated degradation of p57(Kip2) by TGF-beta1/Smad signaling is mediated through a newly synthesized factor(s) that modifies p57(Kip2) or the ubiquitin-proteasome pathway.

Animals↗

A new SUMO-1-specific protease, SUSP1, that is highly expressed in reproductive organs.

A full-length cDNA encoding a SUMO-1-specific protease, named SUSP1, was identified and cloned for the first time from the human brain. Nucleotide sequence analysis of the cDNA containing an open reading frame of 3336 base pairs revealed that the protease consists of 1112 amino acids with a calculated molecular mass of 126,116 Da. Like yeast Ulp1, SUSP1 is a cysteine protease containing the well conserved His/Asp/Cys catalytic triad. SUSP1 expressed in Escherichia coli cells efficiently released SUMO-1 from SUMO-1. beta-galactosidase fusion but not from other ubiquitin-like protein fusions, including Smt3.beta-galactosidase, suggesting its role in the generation of matured SUMO-1 specifically from its precursors. Interestingly, reproductive organs, such as testis, ovary, and prostate, contained much higher amounts of SUSP1 mRNA than colon and peripheral blood leukocyte, whereas other tissues, such as heart and spleen, had little or none. In addition, confocal microscopy using green fluorescent protein.SUSP1 fusion showed that SUSP1 is exclusively localized to the cytoplasm of NIH3T3 and HeLa cells. These results suggest that SUSP1 may play a role in the regulation of SUMO-1-mediated cellular processes particularly related to reproduction.

Amino Acid Sequence↗

Hyperosmolarity-induced gene stimulation is mediated by the negative calcium responsive element.

The negative calcium responsive elements of the parathyroid hormone gene bind to a specific set of nuclear proteins in an extracellular calcium (Ca2+e)-dependent manner. We have found that one of the negative calcium responsive elements, named oligo B, is found in the 5'-flanking region of such vasoactive genes as the vasopressin and atrial natriuretic polypeptide genes. Furthermore, the oligo B-like sequence in the former gene is conserved throughout evolution. Because expression of some of these vasoactive genes is altered by external stimuli which change cell volume, we examined whether oligo B is involved in gene regulation by hyperosmolarity. Here, we demonstrate that the binding between oligo B and its binding nuclear proteins including a redox factor 1 was reduced by hyperosmolarity generated by sodium chloride but not by urea. Such attenuated binding was reversed by dephosphorylating nuclear proteins by a potato acid phosphatase, suggesting that NaCl treatment elicited phosphorylation of these nuclear proteins to weaken their binding activity to oligo B. Furthermore, these nuclear events led to hyperosmolarity-mediated transcriptional stimulation of the genes bearing this DNA element in the cultured cells.

Calcium↗

Evaluation of laser Doppler flowmetry in renal transplantation.

Renal grafts are presently evaluated based on the surgeon's observation of the organ microcirculation. Effectiveness of organ microcirculation has traditionally been accomplished through evaluation of the appearance of the graft. Laser doppler flowmetry (LDF) has been suggested as a possible means to determine graft effectiveness. Renal grafts in 46 transplants were studied using LDF and the technique was evaluated. It was found to be a useful technique for monitoring effectiveness of grafts.

Evaluation Studies as Topic↗

[The clinical significance of albuminuria in renal transplantation].

Urinary excretion of albumin was measured after renal transplantation in 37 patients who received cyclosporine quadrotherapy (cyclosporine A, azathioprine, prednisolone and antilymphocytoglobulin). In 26 patients with a favorable clinical course, daily urinary albumin level increased significantly on the first operative day. Subsequently, it decreased gradually, and remained at about 40mg/day after 3 weeks. In these patients, the urinary albumin level did not correlate with blood pressure, whole blood cyclosporine level, serum creatinine level nor urinary enzyme level, i.e. beta 2-microglobulin, NAG, gamma-GTP. As for correlation between the urinary albumin level and biopsy findings in 21 patients who underwent renal graft biopsy, the urinary albumin level was significantly increased in 5 patients with high degree of lymphocyte infiltration in the renal graft as compared with 16 patients with low degree of infiltration. However, there was no significant correlation between the urinary albumin level and the degree of tubular damage. In 4 patients of allograft rejection, a clinical course was reflected better in the albumin level than in the urinary enzyme level, these results show that the measurement of urinary albumin is a useful clinical examination to evaluate the allograft rejection of renal transplantation in cyclosporine era.

Albuminuria↗