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981.
982.
The mammalian target of rapamycin (mTOR) is essential for skeletal myogenesis through controlling distinct cellular pathways. The importance of the canonical mTOR complex 1 signaling components, including raptor, S6K1, and Rheb, had been suggested in muscle maintenance, growth, and metabolism. However, the role of those components in myogenic differentiation is not entirely clear. In this study we have investigated the functions of raptor, S6K1, and Rheb in the differentiation of C2C12 mouse myoblasts. We find that although mTOR knockdown severely impairs myogenic differentiation as expected, the knockdown of raptor, as well as Rheb, enhances differentiation. Consistent with a negative role for these proteins in myogenesis, overexpression of raptor or Rheb inhibits C2C12 differentiation. On the other hand, neither knockdown nor overexpression of S6K1 has any effect. Moreover, the enhanced differentiation elicited by raptor or Rheb knockdown is accompanied by increased Akt activation, elevated IRS1 protein levels, and decreased Ser-307 (human Ser-312) phosphorylation on IRS1. Finally, IRS1 knockdown eliminated the enhancement in differentiation elicited by raptor or Rheb knockdown, suggesting that IRS1 is a critical mediator of the myogenic functions of raptor and Rheb. In conclusion, the Rheb-mTOR/raptor pathway negatively regulates myogenic differentiation by suppressing IRS1-PI3K-Akt signaling. These findings underscore the versatility of mTOR signaling in biological regulations and implicate the existence of novel mTOR complexes and/or signaling mechanism in skeletal myogenesis. 相似文献
983.
Shin J Chakraborty G Bharatham N Kang C Tochio N Koshiba S Kigawa T Kim W Kim KT Yoon HS 《The Journal of biological chemistry》2011,286(25):22131-22138
984.
985.
Acetohydroxy acid isomeroreductase (AHIR) is a key enzyme in the biosynthesis of branched-chain amino acids. We have determined the first crystal structure of a class I AHIR from Pseudomonas aeruginosa at 2.0 A resolution. Its dodecameric architecture of 23 point group symmetry is assembled of six dimeric units and dimerization is essential for the formation of the active site. The dimeric unit of P.aeruginosa AHIR partially superimposes with a three-domain monomer of spinach AHIR, a class II enzyme. This demonstrates that the so-called plant-specific insert in the middle of spinach AHIR is structurally and functionally equivalent to the C-terminal alpha-helical domain of P.aeruginosa AHIR, and the C-terminal alpha-helical domain was duplicated during evolution from the shorter, class I AHIRs to the longer, class II AHIRs. The dimeric unit of P.aeruginosa AHIR possesses a deep figure-of-eight knot, essentially identical with that in the spinach AHIR monomer. Thus, our work lowers the likelihood of the previous proposal that "domain duplication followed by exchange of a secondary structure element can be a source of such a knot in the protein structure" being correct. 相似文献
986.
4-1BB is an inducible costimulatory molecule that can exert regulatory effects on T cells. Polyclonal antibodies against oligopeptides representing an evolutionarily-conserved region of murine 4-1BB, were prepared and used to stain tissues in normal and inflammatory conditions. The 4-1BB mRNA was detected in the PMA-treated spleen and heart, and constitutively in the brain, kidneys and lungs. The 4-1BB-like protein (BBLP) was expressed on mononuclear cells infiltrating islet cells in the pancreata of NOD mice. Expression was prominent in the early phase of insulitis and the level of expression diminished or disappeared in the later phase. BBLP was identified in the gray matter of brain where neuronal cell bodies, dendrites, and fiber terminals reside but was almost entirely absent in the white matter where axonal fibers dwell. A peculiar rosette pattern was observed in a granular layer of cerebellum and scattered in the stria terminalis. The staining pattern strongly resembled the receptor/nerve terminals in the brain and in the peripheral nervous system. Taken together, BBLP may be associated with the early phase of inflammation and with brain function. 相似文献
987.
988.
Jieun Kim Sung Kyu Lee Yoon Jeon Yehyun Kim Changjin Lee Sung Ho Jeon Jaegal Shim In‐Hoo Kim Seokmann Hong Nayoung Kim Ho Lee Rho Hyun Seong 《The EMBO journal》2014,33(3):217-228
TopBP1 was initially identified as a topoisomerase II‐β‐binding protein and it plays roles in DNA replication and repair. We found that TopBP1 is expressed at high levels in lymphoid tissues and is essential for early lymphocyte development. Specific abrogation of TopBP1 expression resulted in transitional blocks during early lymphocyte development. These defects were, in major part, due to aberrant V(D)J rearrangements in pro‐B cells, double‐negative and double‐positive thymocytes. We also show that TopBP1 was located at sites of V(D)J rearrangement. In TopBP1‐deficient cells, γ‐H2AX foci were found to be increased. In addition, greater amount of γ‐H2AX product was precipitated from the regions where TopBP1 was localized than from controls, indicating that TopBP1 deficiency results in inefficient DNA double‐strand break repair. The developmental defects were rescued by introducing functional TCR αβ transgenes. Our data demonstrate a novel role for TopBP1 as a crucial factor in V(D)J rearrangement during the development of B, T and iNKT cells. 相似文献
989.
Jeongmin Yoon Myung-Han Hyun Jong-Pill Yang Min-Jeong Park Sungsoo Park 《Molecular biology reports》2014,41(6):3867-3879
We performed a systematic review and meta-analysis of the association between the glutathione S-transferase T1 (GSTT1) deletion polymorphism and gastric cancer risk in populations from different ethnic backgrounds, based on a comprehensive literature search of the MEDLINE, EMBASE, and COCHRANE libraries. Thirty-six individual case–control studies comprising 7,689 gastric cancer cases and 12,445 controls were included in our meta-analysis. Overall, the GSTT1 null genotype appeared to increase gastric cancer risk (OR 1.17, 95 % CI 1.06–1.31, p = 0.003). While Caucasian populations showed an association between the GSTT1 deletion polymorphism and gastric cancer risk (OR 1.27, 95 % CI 1.05–1.52, p = 0.01), Asian populations did not show such an association (p = 0.11). When stratified by quality assessment scores, a significant association between the GSTT1 deletion polymorphism and gastric cancer risk was observed only in the Caucasian high quality subgroup (OR 1.27 95 % CI 1.01–1.60, p = 0.05). Null genotypes for both GSTT1 and GSTM1 deletion polymorphisms also increased gastric cancer risk (OR 1.37, 95 % CI 1.04–1.80, p = 0.03). Our study suggests that the GSTT1 null genotype is associated with a significant increase in gastric cancer risk in Caucasians, but not in Asians. Further well-designed studies are required to confirm the association between GSTT1 polymorphisms and gastric cancer risk in relation to various clinicopathological factors in different ethnic groups, especially Caucasians. 相似文献
990.