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Click to add to Selected Topics* Пролиферация гепатоцитов: Rb vs YAP

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 old post 11.08.2014 21:39     Report Post  Report Post for topic curator       Personal message  Send an e-mail

Attached ImageOrgan_Size_Control_Is_Dominant_over_Rb_Family_Inactivation.jpgБелки семейства Rb (от Retinoblastoma) являются ключевыми регуляторами клеточного цикла, запрещая переход от G0 к G1. Они связываются с транскрипционным фактором E2F, регулируя экспрессию ряда генов клеточного цикла. Инактивация Rb приводит к неконтролируемой пролиферации и инициации онкогенеза. Неудивительно, что гены Rb оказываются мутированными в клетках самых разных опухолей. Однако, как выяснилось, "всевластие" Rb оказалось не столь безгранично, как считалось ранее.

Статья в Cell Reports посвящена роли Rb в регуляции пролиферации гепатоцитов. Печень млекопитающих примечательна необычно высокой способностью к регенерации, в том числе и после частичной гепатэктомии. Поэтому, вследствие высокого пролиферативного потенциала, гепатоциты являются хорошей моделью для изучения регуляции клеточного цикла. Исследователи провели кондиционный нокаут всех трех генов семейства Rb в гепатоцитах взрослых мышей – Rb, p107 и p130 (TKO, triple-knockout). К удивлению авторов, TKO в зрелых гепатоцитах (в отличие от предшественников оных) привел лишь к временной активации пролиферации – через некоторое время клетки опять переставали делиться. Это означает, что активность Rb является не единственным механизмом ареста клеточного цикла зрелых гепатоцитов. Дальнейшее изучение этого феномена показало, что прекращение пролиферации не зависит от p53-пути, а находится под контролем E2F. Сравнение транскриптомов покоящихся клеток дикого типа и "арестованных" TKO показало, что значительная часть генов, экспрессия которых оказалась подавлена в TKO-гепатоцитах, является мишенями YAP. YAP – транскрипционный фактор, ключевой участник сигнального каскада Hippo, играющего важную роль в эмбриональном развитии печени, контроле ее размера и онкогенной трансформации. Был отмечен пониженный уровень YAP и TEAD1, а также повышенный уровень фосфорилирования YAP. Выяснилось, что E2F и YAP регулируют сходный набор генов-мишеней. Трансформация TKO-гепатоцитов конститутивно-активной формой YAP приводила к активации генов-мишеней E2F и возобновлению пролиферации. Детали этого механизма не вполне ясны; предполагается, что E2F и YAP могут физически взаимодействовать на промоторах генов-мишеней.

Таким образом, в гепатоцитарных предшественниках пролиферативная активность контролируется белками семейства Rb. В зрелых же гепатоцитах вступает в игру Hippo-зависимый контроль размера органов, образуя дополнительный механизм контроля клеточного деления.

Источник:
Ehmer et al. Organ Size Control Is Dominant over Rb Family Inactivation to Restrict Proliferation In Vivo. Cell Rep. 2014 Jul 24;8(2):371-81.
Картинка – graphical abstract к обсуждаемой статье.
Статья в открытом доступе.


Number of thanks: 3These members thanked the author (3): Vadim Sharov, Пасюк, hadw



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 old post 29.08.2014 11:24     Report Post  Report Post for topic curator     
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"YAP – транскрипционный фактор" ©

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(Guest @ 29.08.2014 11:24)
Link to the original post  "YAP – транскрипционный фактор" ©

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http://www.ncbi.nlm.nih.gov/pmc/articles/P...l00018-0175.pdf

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почитал Материалы и Методы smile.gif

РНК-Сек на ливере а не на гепатоцитах Хисеком2000 с неправильной биоинформатикой

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Чип-Сек не делали а содрали данные с китайцев для YAP , E2F сослались на типа

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"Детали этого механизма не вполне ясны; предполагается, что Е2Ф и ЯП могут физически взаимодействовать на промоторах генов-мишеней." (ц) smile.gif

ставится Чип-Сек на коактиватор YAP на мышиных ливерах - потом Де ново мотив
серч MEME-CHIP на потенциальных Трансфаков-партнеров а не строить гипотезы smile.gif
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(Guest @ 29.08.2014 14:16)
Link to the original post  "Детали этого механизма не вполне ясны; предполагается, что Е2Ф и ЯП могут физически взаимодействовать на промоторах генов-мишеней." (ц) smile.gif

ставится Чип-Сек на коактиватор  YAP              на мышиных ливерах - потом Де ново мотив
серч      MEME-CHIP                  на потенциальных Трансфаков-партнеров а не строить гипотезы smile.gif

http://www.ncbi.nlm.nih.gov/pmc/articles/P...6-8935-6-30.pdf
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(Guest @ 29.08.2014 13:22)
Link to the original post  почитал Материалы и Методы smile.gif

РНК-Сек на ливере а не на гепатоцитах Хисеком2000 с неправильной биоинформатикой

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http://www.nature.com/nprot/journal/v8/n9/...t.2013.099.html
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 old post Post on English  06.02.2021 12:30     Report Post  Report Post for topic curator     
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 old post Post on English  05.04.2021 09:36     Report Post  Report Post for topic curator       Personal message
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 old post Post on English  07.04.2021 09:40     Report Post  Report Post for topic curator     
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 old post Post on English  07.04.2021 09:40     Report Post  Report Post for topic curator     
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 old post Post on English  07.04.2021 09:40     Report Post  Report Post for topic curator     
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 old post Post on English  07.04.2021 09:41     Report Post  Report Post for topic curator     
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 old post Post on English  07.04.2021 09:41     Report Post  Report Post for topic curator     
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 old post Post on English  07.04.2021 09:41     Report Post  Report Post for topic curator     
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 old post Post on English  07.04.2021 09:42     Report Post  Report Post for topic curator     
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 old post Post on English  07.04.2021 09:42     Report Post  Report Post for topic curator     
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 old post Post on English  07.04.2021 09:43     Report Post  Report Post for topic curator     
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 old post Post on English  07.04.2021 09:43     Report Post  Report Post for topic curator     
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 old post Post on English  07.04.2021 09:45     Report Post  Report Post for topic curator     
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 old post Post on English  07.04.2021 09:46     Report Post  Report Post for topic curator     
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 old post Post on English  07.04.2021 09:46     Report Post  Report Post for topic curator     
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 old post Post on English  07.04.2021 09:46     Report Post  Report Post for topic curator     
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 old post Post on English  27.09.2021 17:01     Report Post  Report Post for topic curator       Personal message  Send an e-mail
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 old post Post on English  17.10.2021 15:47     Report Post  Report Post for topic curator       Personal message  Send an e-mail
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 old post Post on English  28.10.2021 02:56     Report Post  Report Post for topic curator       Personal message  Send an e-mail
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 old post Post on English  28.10.2021 18:45     Report Post  Report Post for topic curator       Personal message  Send an e-mail
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