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清华大学研究组揭示TRIM33蛋白的新功能

已有 7336 次阅读 2017-9-25 15:31 |个人分类:《中国科学》论文|系统分类:论文交流

近日,清华大学郗乔然研究组发文揭示了TRIM33蛋白胚胎干细胞早期分化过程中发挥作用的新模式,即TRIM33蛋白并非通过为学界所熟知的RING保守结构域来调控WNT信号通路,而是通过PHD-Bromo结构域发挥功能。论文“Role of TRIM33 in Wnt signaling during mesendoderm differentiation”在线发表于SCIENCE CHINA Life Sciences(《中国科学:生命科学》英文版)

TRIM(tripartitemotif family)蛋白超家族目前有超过70个蛋白成员,它们参与了广泛的生物过程。这类蛋白的异常表达往往会引起很多病理异常,包括发育异常、神经退行性疾病、病毒感染及癌症。这类蛋白结构的共同之处在于都有三个保守的结构域,包括RING结构域、两个B-box结构域和一个螺旋结构域。因为RING结构域的存在,TRIM超家族很多成员被认为有泛素化E3连接酶的功能。

TRIM33蛋白TRIM蛋白超家族的一员,除包含三个保守结构域之外,在羧基端还具有PHD指环结构域和Bromo结构域。有研究表明,TRIM33蛋白具有抑癌因子功能,可以作为泛素化E3连接酶降解脑胶质瘤及肠癌细胞核内的β-catenin蛋白,抑制WNT信号通路。该功能是通过其RING结构域来实现的。同时,TRIM33蛋白具有转录因子功能,能够通过PHD-Bromo结构域识别特定的组蛋白修饰(染色质阅读器),在胚胎干细胞早期分化过程中参与TGF-β信号通路调控。

   在小鼠胚胎干细胞中,尽管TRIM33蛋白能够与β-catenin蛋白相互作用,但是过表达或者敲除TRIM33蛋白并不影响核内β-catenin蛋白表达水平。并且,荧光色素酶报告系统结果显示,TRIM33蛋白并不影响整体的WNT/TCF信号通路活性。进一步的研究表明,敲除TRIM33蛋白显著抑制了早期胚胎发育过程中一些重要的WNT靶基因如Mixl1的表达。TRIM33蛋白依赖其染色质阅读器功能参与胚胎干细胞早期分化过程,在转录水平特异调控与分化相关的调控因子,而非影响整体WNT通路的活性。这意味着,TRIM33蛋白的功能发挥依赖于细胞特异性,在不同的细胞中,它可以通过不同的结构域发挥不同的功能。这对于解析在不同病理条件下TRIM33蛋白如何发挥功能提供了更具体的线索。


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"...the dreams of a visionary mind to be closer to reality than the common sense judgment of  the realists." 闂佹寧鍐婚幏锟� Car-Gustaf Arvid Rossby
IP: 202.113.11.*   闂佹悶鍎抽崑娑⑺囬敓锟� | 闁荤姍宥嗗 闁荤姍宥嗗 +1 [9]闂佸搫顦崝宥夘敆濠婂牊鍋ら柨鐕傛嫹   2023-7-20 19:37
闂佺偨鍎茬划蹇曟崲濞嗘垶鍠嗗ù锝埿掗崑鎾诲川椤撴粈绮撻梺鐓庣摠閸ㄦ娊鎳欓幋锔藉剭闁告洦鍏橀崣娲煙椤栨繃鐝柣锔诲櫍閹娊寮剁捄銊︽緰婵炴垶鎹侀濠勭不閻斿吋鍤€闁告侗鍨遍悾閬嶆偨椤栨稓鎽冮柣锔藉灴瀹曟岸濡堕崱妯煎姺闂佸搫娲ら悺銊ф暜鐎涙ɑ浜ら柟瀵稿У閸╁倿鎮楅崷顓炰杭闁逞屽墮閸婄敻鍩€椤掑﹥瀚� 闂佹寧鍐婚幏锟� 缂傚倸鍟〃鍡涘蓟婢跺本瀚婚柨鐕傛嫹

"...the dreams of a visionary mind to be closer to reality than the common sense judgment of  the realists." 闂佹寧鍐婚幏锟� Car-Gustaf Arvid Rossby
IP: 202.113.11.*   闂佹悶鍎抽崑娑⑺囬敓锟� | 闁荤姍宥嗗 闁荤姍宥嗗 +1 [8]闂佸搫顦崝宥夘敆濠婂牊鍋ら柨鐕傛嫹   2023-7-9 21:00
[1] 闁荤姍鍥ㄦ锭缂佺姴绉剁划鈺呮晸閿燂拷, 濠电偛鑻悧蹇涳綖閹版澘瀚夐柨鐕傛嫹. 闂佸搫鐗滈崜娑綖閺嶎灝鎺楀即濮樿京鎳濋梺姹囧灮閸犲秶绮╃€涙ɑ濯存繝濠傚暙缁茬瘶ature闂佹寧绋戦惉鑲┾偓姘煎幘缁晝鈧綆浜為弳姘舵煙鏉堢偓瀚�9闂佺懓鐡ㄩ崝鏇熷閹邦厽濯存繝濠傜墕濞咃拷. 缂備礁顦伴崹鐢割敆閻旇櫣纾鹃柟鎼灣缁€锟�2023-07-08
https://news.sciencenet.cn/htmlnews/2023/7/504367.shtm

[2] Kaifeng Bi, Lingxi Xie, Hengheng Zhang, Xin Chen, Xiaotao Gu & Qi Tian. Accurate medium-range global weather forecasting with 3D neural networks [J]. Nature, 2023-07-05
doi:  10.1038/s41586-023-06185-3
https://www.nature.com/articles/s41586-023-06185-3

[3] Kaifeng Bi, Lingxi Xie, Hengheng Zhang, Xin Chen, Xiaotao Gu, Qi Tian. Pangu-Weather: A 3D High-Resolution Model for Fast and Accurate Global Weather Forecast. 2022-11-03
doi:  10.48550/arXiv.2211.02556
https://arxiv.org/abs/2211.02556

[4] 闁荤姴顑冮崹褰掑闯閻戣棄鍗抽柨鐕傛嫹​闂佹寧鍐婚幏锟�2023-07-06闂佹寧绋戦惉鐓庘枍閵夛妇鈻斿┑鍌涚煒ture濠殿喗绻愮徊浠嬪垂閺冨牆违濞达綀顕栭崕灞剧箾閹绘帒绾ч柣銊ф暩閹告帡鍨鹃懠璺哄箑闂婎偄娲ら崯鎶藉磿濡や胶鈻曢柨鏃囥€€閸嬫挻鎷呴幋鎺撳攭闂備焦褰冪换鎺擃殽閸ヮ剙妫橀悷娆忓閺€鎶芥煕濞嗘劕鐏ョ紒鏃傚厴閺佸秴顫濇潏銊э紭闂佸憡鐟i崐鏍儍閻㈠灚瀵柍銉у仺娴滐絾淇婇妞诲亾瀹曞洠鍋撻悜钘夎Е閹艰揪绲块弫楣冨级閳哄倻鈽夐柣顐㈢Ф缁辨帡鎳濋弶璺ㄥ
https://zhuanlan.zhihu.com/p/641851617

[5] 闁荤姴顑冮崹褰掑闯閻戣棄鍗抽柨鐕傛嫹​闂佹寧鍐婚幏锟�2022-11-10闂佹寧绋戦懟顖氱暦閺囩喓鈻旈弶鐐村闂呮﹢鏌熺紒妯哄闁搞値鍙冮幆鍕熼崫鍕▕濠殿喗蓱濡線鎸呴崟顒€绶炵憸搴ゅ暞闂佹悶鍔岄鎴犳閻楀牏鈻旀い鎾卞灪濮f劙鏌¢崼銏犳瀾闁汇劎鏁搁幐鎺楁晸閻欌偓閺嗘洟鏌熼煬鎻掑姢缂併劍瀵ч幆鏃堟晝閸屻倖绂冨┑鐐叉灤閵堝泦銏ゅ级閳轰焦鐭楃紒鍗炲缁辨帡鎮㈤崨濠冾啀闂佺ǹ锕ら崥瀣蓟閻斿皝鏋栭柡鍥朵簽缁€澶愭⒑椤愩倕鏋庨悗瑙勫▕楠炴捇骞囬鈧壕锟�10000闂佺ǹ锕ょ粔铏閹烘挾鈻旈柨鐕傛嫹
https://zhuanlan.zhihu.com/p/582285853
IP: 202.113.11.*   闂佹悶鍎抽崑娑⑺囬敓锟� | 闁荤姍宥嗗 闁荤姍宥嗗 +1 [7]闂佸搫顦崝宥夘敆濠婂牊鍋ら柨鐕傛嫹   2023-7-7 17:08
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Verification of the high-resolution (HRES) forecast of surface parameters
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ECMWF
  
European Centre for Medium-Range Weather Forecast
  
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Verification of the high-resolution forecast of surface parameters
Verification of high-resolution forecasts
  
https://apps.ecmwf.int/webapps/opencharts/products/plwww_m_hr_wp_ts?parameter=10m%20wind%20direction


10 m wind direction
IP: 202.113.11.*   闂佹悶鍎抽崑娑⑺囬敓锟� | 闁荤姍宥嗗 闁荤姍宥嗗 +1 [4]闂佸搫顦崝宥夘敆濠婂牊鍋ら柨鐕傛嫹   2021-7-29 17:38
Verification of the high-resolution forecast of surface parameters

Verification of the high-resolution forecast of surface parameters
Verification of high-resolution forecasts
  
Verification of the high-resolution forecast of surface parameters against SYNOP observations.
© European Centre for Medium-Range Weather Forecasts

https://apps.ecmwf.int/webapps/opencharts/products/plwww_m_hr_wp_ts?parameter=10m%20wind%20speed
IP: 220.160.125.*   闂佹悶鍎抽崑娑⑺囬敓锟� | 闁荤姍宥嗗 闁荤姍宥嗗 +1 [3]閻庢鍠氭慨瀵告崲閸岀偛妫橀柨鐕傛嫹   2018-7-24 10:49
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IP: 202.113.11.*   闂佹悶鍎抽崑娑⑺囬敓锟� | 闁荤姍宥嗗 闁荤姍宥嗗 +1 [2]闂佸搫顦崝宥夘敆濠婂牊鍋ら柨鐕傛嫹   2018-7-23 23:57
Next, both models differ in availability.  GFS runs 4 times a day, ECMWF runs twice a day.  This means GFS has the opportunity to recover from bad forecasts (say, due to bad input data) by producing more per day.  ECMWF generally outperforms GFS, but if one of the forecast runs was bad, you've got to wait longer for new data.  The reason for the difference in availability is due to the time it takes to compute the model.  Nonhydrostatic models are more computationally expensive, which is why ECMWF is the only global nonhydrostatic model used for operation meteorology.

GFS is free, ECMWF is not. You can get the latest GFS runs for free from NCEP (http://www.ncep.noaa.gov/).  You can even download the model and run it on your home super computer if you are so inclined (http://www.nco.ncep.noaa.gov/pmb...).  To get ECMWF data, you typically need to be affiliated with some organization that pays for it.

Both models produce different products. You will probably be able to get the typic...
IP: 202.113.11.*   闂佹悶鍎抽崑娑⑺囬敓锟� | 闁荤姍宥嗗 闁荤姍宥嗗 +1 [1]闂佸搫顦崝宥夘敆濠婂牊鍋ら柨鐕傛嫹   2018-7-23 23:56
What is the difference between the ECMWF, GFS, and other weather forecasting models?
https://www.quora.com/What-is-the-difference-between-the-ECMWF-GFS-and-other-weather-forecasting-models
   
here's a lot of differences between numerical models, so I'll just (briefly) mention the differences between GFS and ECMWF.
  
First both are global models, meaning they produce a forecast for the entire world.  There are also regional models like MM5, NAM, and WRF that produce forecasts specific to a region at a high resolution (I'll talk about resolution later).  Regional models tend to seed their forecasts from global models; GFS provides context for MM5.  I'm not sure what regional models use ECMWF, but I'm sure there are quite a few.
  
GFS and ECMWF use different equations for predicting atmospheric conditions.  GFS is a hydrostatic model and ECMWF is nonhydrostatic.  Hydrostatic models use pressure as vertical coordinates in the forecast (e.g. make forecasts at specific isobars) and ess...

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