Pneumocystis carinii contains a functional cell-division-cycle Cdc2 homologue.
Pneumocystis carinii contains a functional cell-division-cycle Cdc2 homologue.
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卡氏肺囊虫含有功能性细胞分裂周期 Cdc2 同源物。
DOI：
10.1165/ajrcmb.18.3.3122
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发表时间：
1998
期刊：
影响因子：
--
通讯作者：
Limper,AH
中科院分区：
文献类型：
--
作者：
Thomas,CF;Anders,RA;Gustafson,MP;Leof,EB;Limper,AH
卡氏肺孢子虫在免疫功能低下的患者中引起危及生命的肺炎。无法培养P。Carinii阻碍了对生物体生命周期的基础研究，限制了针对它的新疗法的开发。最近的研究表明，P。卡氏裂殖酵母是一种真菌，与其他子囊菌如裂殖酵母有亲缘关系。细胞以OFS为周期。Pombeby和同源真菌受到细胞分裂周期分子(CDC)的仔细调控，特别是细胞分裂周期2(CDc2)，这是一种丝氨酸苏氨酸激酶，在G1限制点具有必要的活性，并进入有丝分裂。抗proline–serine–threonine–alanine–isoleucine–arginine(PSTAIR)蛋白中保守的氨基酸序列抗体是从P。Carinii萃取物，一种具有与类Cdc2蛋白一致的激酶活性的分子。在其所在生物体的整个生命周期中，Cdc2分子表现出不同的活性。与此相一致，Thep.CariniiCdc2在INP中表现出较高的比活性。营养核型(滋养体)比孢子壳形式(包囊)好。此外，完整的基因组和互补DNA(CDNA)序列OFP。CariniiCDc2与其他病原真菌的相应序列同源性最高。函数OFP。Carinii cdc2cDNA通过与突变株OFS的DNA互补而被进一步证实。对温度敏感的Cdc2活性缺乏的庞贝。塞普。Carinii cdc2c DNA在这些突变株OFS中恢复了正常的cdc2功能。Pombe，并促进真菌增殖。这些研究是对细胞周期调节机制INP的第一次分子分析。卡里尼。进一步了解OFP。Carinii的生命周期为预防和治疗它在免疫功能低下患者中引起的难治性感染提供了新的见解。
Pneumocystis cariniicauses life-threatening pneumonia in immunocompromised patients. The inability to cultureP. cariniihas hampered basic investigations of the organism's life cycle, limiting the development of new therapies directed against it. Recent investigations indicate thatP. cariniiis a fungus phylogenetically related to other ascomycetes such asSchizosaccharomyces pombe. The cell cycles ofS. pombeand homologous fungi are carefully regulated by cell-division-cycle molecules (cdc), particularly cell-division-cycle 2 (Cdc2), a serine–threonine kinase with essential activity at the G1restriction point and for entry into mitosis. Antibodies to the proline–serine–threonine–alanine–isoleucine–arginine (PSTAIR) amino-acid sequence conserved in Cdc2 proteins specifically precipitated, fromP. cariniiextracts, a molecule with kinase activity consistent with a Cdc2-like protein. Cdc2 molecules exhibit differential activity throughout the life cycle of the organisms in which they occur. In accord with this, theP. cariniiCdc2 showed greater specific activity inP. cariniitrophic forms (trophozoites) than in spore-case forms (cysts). In addition, complete genomic and complementary DNA (cDNA) sequences ofP. cariniiCdc2 were cloned and found to be most closely homologus to the corresponding sequences of other pathogenic fungi. The function ofP. carinii cdc2cDNA was further documented through its ability to complement the DNA of mutant strains ofS. pombewith temperature-sensitive deficiencies in Cdc2 activity. TheP. carinii cdc2cDNA restored normal Cdc2 function in these mutant strains ofS. pombe, and promoted fungal proliferation. These studies represent the first molecular analysis of the cell-cycle-regulatory machinery inP. carinii. Further understanding ofP. carinii's life cycle promises novel insights for preventing and treating the intractable infection it causes in immunocompromised patients.