Leaves play a key role in photosynthesis in rice plants. The premature senescence of such plants directly reduces the accumulation of photosynthetic products and also affects yield and grain quality significantly and ...Leaves play a key role in photosynthesis in rice plants. The premature senescence of such plants directly reduces the accumulation of photosynthetic products and also affects yield and grain quality significantly and negatively. A novel premature senescence mutant, mps1（mid-late stage premature senescence 1）, was identified from a mutant library consisting of ethyl methane sulfonate（EMS） induced descendants of Jinhui 10, an elite indica restorer line of rice. The mutant allele, mps1, caused no phenotypic differences from the wild type（WT）, Jinhui 10, but drove the leaves to turn yellow when mutant plants grew to the tillering stage, and accelerated leaf senescence from the filling stage to final maturation. We characterized the agronomic traits, content of photosynthetic pigments and photosynthetic efficiency of mps1 and WT, and fine-mapped MPS1. The results showed that the MPS1-drove premature phenotype appeared initially on the leaf tips at the late tillering stage and extended to the middle of leaves during the maturing stage. Compared to the WT, significant differences were observed among traits of the number of grains per panicle（–31.7%） and effective number of grains per panicle（–38.5%） of mps1 individuals. Chlorophyll contents among the first leaf from the top（Top 1st）, the second leaf from the top（Top 2nd） and the third leaf from the top（Top 3rd） of mps1 were significantly lower than those of WT（P〈0.05）, and the levels of photosynthetic efficiency from Top 1st to the forth leaf from the top（Top 4th） of mps1 were significantly lower than those of WT（P〈0.01）. Results from the genetic analysis indicated that the premature senescence of mps1 is controlled by a recessive nuclear gene, and this locus, MPS1 is located in a 37.4-kb physical interval between the markers Indel145 and Indel149 on chromosome 6. Genomic annotation suggested eight open reading frames（ORFs） within this physical region. All of these results will provide informative references for th展开更多
Error-free mitosis depends on accurate chromosome attachment to spindle microtubules,which is monitored by the spindle assembly checkpoint(SAC)signaling.As an upstream factor of SAC,the precise and dynamic kinetochore...Error-free mitosis depends on accurate chromosome attachment to spindle microtubules,which is monitored by the spindle assembly checkpoint(SAC)signaling.As an upstream factor of SAC,the precise and dynamic kinetochore localization of Mps1 kinase is critical for initiating and silencing SAC signaling.However,the underlying molecular mechanism remains elusive.Here,we demonstrated that the multisite interactions between Mps1 and Ndc80 complex(Ndc80C)govern Mps1 kinetochore targeting.Importantly,we identified direct interaction between Mps1 tetratricopeptide repeat domain and Ndc80C.We further identified that Mps1 C-terminal fragment,which contains the protein kinase domain and C-tail,enhances Mps1 kinetochore localization.Mechanistically,Mps1 C-terminal fragment mediates its dimerization.Perturbation of C-tail attenuates the kinetochore targeting and activity of Mps1,leading to aberrant mitosis due to compromised SAC function.Taken together,our study highlights the importance of Mps1 dimerization and multisite interactions with Ndc80C in enabling responsive SAC signaling.展开更多
Purpose:The metallopanstimulin-1(MPS-1)gene is a growth factor-inducible gene,which is highly expressed in many human cancers and may be involved in the progression towards tumor malignancy.However,it is unclear wheth...Purpose:The metallopanstimulin-1(MPS-1)gene is a growth factor-inducible gene,which is highly expressed in many human cancers and may be involved in the progression towards tumor malignancy.However,it is unclear whether MPS-1 plays any role in gastric cancer development or progression.Our studies were designed to clarify the MPS-1 expression pattern and to explore its potential role in gastric cancer.Experimental Design:The expression pattern of MPS-1 was determined in primary gastric cancer specimens and gastric cancer cell lines via immunohistochemistry and Western blotting.To investigate the functional significance of MPS-1 expression,three small interfering RNA(siRNA)expression plasmids were constructed and transfected into gastric cancer cell line SGC7901.The stable cell lines transfected with the siRNA targeting MPS-1 mRNA plasmids were selected and the biological features of these cells were examined.Results:MPS-1 was overexpressed in 86% of the gastric cancer tissues and all gastric cancer cells.In addition,MPS-1 expression was significantly increased and corresponded with the tumor-node-metastasis clinical stage,and was significantly higher in the late stage(P<0.01).The MPS-1 expression level was significantly decreased in the transfected cells with MPS-1-specific siRNA expression plasmid pRNAT-133.Furthermore,the stable transfected cancer cells exhibited an increase in the incidence of spontaneous apoptosis and a decrease in growth ability and tumorigenicity in nude mice.Conclusions:These results provide strong evidence that MPS-1 plays an important role in gastric cancer cell proliferation and development,and suggests that MPS-1 is a promising target for gastric cancer treatment.展开更多
基金supported by grants from the National Natural Science Foundation of China(31371597)the Fundamental Research Funds for the Central Universities,Ministry of Education of China(XDJK2014C147)the Chongqing Key Laboratory Capacity Upgrade Program of China(cstc-2014pt-sy80001)
文摘Leaves play a key role in photosynthesis in rice plants. The premature senescence of such plants directly reduces the accumulation of photosynthetic products and also affects yield and grain quality significantly and negatively. A novel premature senescence mutant, mps1（mid-late stage premature senescence 1）, was identified from a mutant library consisting of ethyl methane sulfonate（EMS） induced descendants of Jinhui 10, an elite indica restorer line of rice. The mutant allele, mps1, caused no phenotypic differences from the wild type（WT）, Jinhui 10, but drove the leaves to turn yellow when mutant plants grew to the tillering stage, and accelerated leaf senescence from the filling stage to final maturation. We characterized the agronomic traits, content of photosynthetic pigments and photosynthetic efficiency of mps1 and WT, and fine-mapped MPS1. The results showed that the MPS1-drove premature phenotype appeared initially on the leaf tips at the late tillering stage and extended to the middle of leaves during the maturing stage. Compared to the WT, significant differences were observed among traits of the number of grains per panicle（–31.7%） and effective number of grains per panicle（–38.5%） of mps1 individuals. Chlorophyll contents among the first leaf from the top（Top 1st）, the second leaf from the top（Top 2nd） and the third leaf from the top（Top 3rd） of mps1 were significantly lower than those of WT（P〈0.05）, and the levels of photosynthetic efficiency from Top 1st to the forth leaf from the top（Top 4th） of mps1 were significantly lower than those of WT（P〈0.01）. Results from the genetic analysis indicated that the premature senescence of mps1 is controlled by a recessive nuclear gene, and this locus, MPS1 is located in a 37.4-kb physical interval between the markers Indel145 and Indel149 on chromosome 6. Genomic annotation suggested eight open reading frames（ORFs） within this physical region. All of these results will provide informative references for th
文摘目的明确癌基因B-RafV600E在Mps1和B-RafWT/MEK/ERK通路之间自动调节的负反馈回路中抵抗作用的具体机制。方法 (1)Sbcl2转染B-RafWT和Mps1-KD,Western blot方法检测p-ERK水平;(2)向B-Raf野生型SK-MEL31、Sbcl2、WM35细胞及V600E突变型SK-MEL28、A375细胞中过表达Mps1,Western blot方法检测p-ERK水平;(3)在SK-MEL31、Sbcl2、WM35细胞中敲低AKT,转染Mps1,Western blot方法检测p-ERK水平;(4)在SK-MEL31、Sbcl2、WM35细胞中敲低内源性B-Raf,过表达外源性RafV600E,Western blot方法检测p-AKT水平;敲低SK-MEL-28、A375细胞中RafV600E,Western blot方法检测p-A K T水平。结果 (1)M p s 1激酶和B-RafWT/MEK/ERK通路之间的自动负反馈通路不依赖Mps1激酶的活性;(2)在野生型SK-MEL31、Sbcl2、WM35细胞中外源性Mps1的表达可诱导AKT磷酸化,抑制ERK活性;V600E突变型SK-MEL28、A375细胞中外源性Mps1的表达不能诱导AKT磷酸化,亦不影响ERK活性。(3)敲低野生型黑色素瘤细胞中的AKT后,Mps1和B-RafWT/MEK/ERK之间的负反馈作用消失。(4)癌基因B-RafV600E通过抑制AKT的磷酸化,进而抵抗Mps1激酶与B-Raf/MEK/ERK通路之间的负反馈调节作用。结论 Mps1和B-RafWT/MEK/ERK通路之间的自动负反馈通路不依赖Mps1激酶的活性,且癌基因B-RafV600E对B-Raf/MEK/ERK/Mps1负反馈通路的抵抗作用是通过抑制AKT的磷酸化实现的。
基金supported by the National Key R&D Program of China(2017YFA 0102900 and 2017 YFA 0503600)the National Natural Science Fondation of China(31671407 and 31871359 to Z.D.+4 种基金31621002,31430054,91854203,and 31320103904 to X.Y.31301099 and 21672201 to X.G.31471275 to D.W.),Strategic Priority Research Program of the Chinese Academy of Sciences(XDB19040000)Chinese Academy of Sciences Center for Excellence in Molecular Cell Science(2015 HSC-UE010)MOE Innovative Team(IRT_17R102).
文摘Error-free mitosis depends on accurate chromosome attachment to spindle microtubules,which is monitored by the spindle assembly checkpoint(SAC)signaling.As an upstream factor of SAC,the precise and dynamic kinetochore localization of Mps1 kinase is critical for initiating and silencing SAC signaling.However,the underlying molecular mechanism remains elusive.Here,we demonstrated that the multisite interactions between Mps1 and Ndc80 complex(Ndc80C)govern Mps1 kinetochore targeting.Importantly,we identified direct interaction between Mps1 tetratricopeptide repeat domain and Ndc80C.We further identified that Mps1 C-terminal fragment,which contains the protein kinase domain and C-tail,enhances Mps1 kinetochore localization.Mechanistically,Mps1 C-terminal fragment mediates its dimerization.Perturbation of C-tail attenuates the kinetochore targeting and activity of Mps1,leading to aberrant mitosis due to compromised SAC function.Taken together,our study highlights the importance of Mps1 dimerization and multisite interactions with Ndc80C in enabling responsive SAC signaling.
基金Hi-Tech Research and Development Program of China-"863"Program,2002CB713700National Basic ResearchProgram of China-"973"Program,2002CB713700.
文摘Purpose:The metallopanstimulin-1(MPS-1)gene is a growth factor-inducible gene,which is highly expressed in many human cancers and may be involved in the progression towards tumor malignancy.However,it is unclear whether MPS-1 plays any role in gastric cancer development or progression.Our studies were designed to clarify the MPS-1 expression pattern and to explore its potential role in gastric cancer.Experimental Design:The expression pattern of MPS-1 was determined in primary gastric cancer specimens and gastric cancer cell lines via immunohistochemistry and Western blotting.To investigate the functional significance of MPS-1 expression,three small interfering RNA(siRNA)expression plasmids were constructed and transfected into gastric cancer cell line SGC7901.The stable cell lines transfected with the siRNA targeting MPS-1 mRNA plasmids were selected and the biological features of these cells were examined.Results:MPS-1 was overexpressed in 86% of the gastric cancer tissues and all gastric cancer cells.In addition,MPS-1 expression was significantly increased and corresponded with the tumor-node-metastasis clinical stage,and was significantly higher in the late stage(P<0.01).The MPS-1 expression level was significantly decreased in the transfected cells with MPS-1-specific siRNA expression plasmid pRNAT-133.Furthermore,the stable transfected cancer cells exhibited an increase in the incidence of spontaneous apoptosis and a decrease in growth ability and tumorigenicity in nude mice.Conclusions:These results provide strong evidence that MPS-1 plays an important role in gastric cancer cell proliferation and development,and suggests that MPS-1 is a promising target for gastric cancer treatment.
