FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2094837086> ?p ?o ?g. }

• W2094837086 endingPage "e104444" @default.
• W2094837086 startingPage "e104444" @default.
• W2094837086 abstract "MDM2 and MDMX are the chief negative regulators of the tumor-suppressor protein p53 and are essential for maintaining homeostasis within the cell. In response to genotoxic stress and also in several cancer types, MDM2 and MDMX are alternatively spliced. The splice variants MDM2-ALT1 and MDMX-ALT2 lack the p53-binding domain and are incapable of negatively regulating p53. However, they retain the RING domain that facilitates dimerization of the full-length MDM proteins. Concordantly, MDM2-ALT1 has been shown to lead to the stabilization of p53 through its interaction with and inactivation of full-length MDM2. The impact of MDM2-ALT1 expression on the p53 pathway and the nature of its interaction with MDMX remain unclear. Also, the role of the architecturally similar MDMX-ALT2 and its influence of the MDM2-MDMX-p53 axis are yet to be elucidated. We show here that MDM2-ALT1 is capable of binding full-length MDMX as well as full-length MDM2. Additionally, we demonstrate that MDMX-ALT2 is able to dimerize with both full-length MDMX and MDM2 and that the expression of MDM2-ALT1 and MDMX-ALT2 leads to the upregulation of p53 protein, and also of its downstream target p21. Moreover, MDM2-ALT1 expression causes cell cycle arrest in the G1 phase in a p53 and p21 dependent manner, which is consistent with the increased levels of p21. Finally we present evidence that MDM2-ALT1 and MDMX-ALT2 expression can activate subtly distinct subsets of p53-transcriptional targets implying that these splice variants can modulate the p53 tumor suppressor pathway in unique ways. In summary, our study shows that the stress-inducible alternative splice forms MDM2-ALT1 and MDMX-ALT2 are important modifiers of the p53 pathway and present a potential mechanism to tailor the p53-mediated cellular stress response." @default.
• W2094837086 created "2016-06-24" @default.
• W2094837086 creator A5006365668 @default.
• W2094837086 creator A5013409482 @default.
• W2094837086 creator A5015468004 @default.
• W2094837086 creator A5041373734 @default.
• W2094837086 creator A5053533470 @default.
• W2094837086 creator A5058937676 @default.
• W2094837086 creator A5079702465 @default.
• W2094837086 date "2014-08-08" @default.
• W2094837086 modified "2023-09-26" @default.
• W2094837086 title "Stress-Induced Alternative Splice Forms of MDM2 and MDMX Modulate the p53-Pathway in Distinct Ways" @default.
• W2094837086 cites W1563316806 @default.
• W2094837086 cites W1575363584 @default.
• W2094837086 cites W1576330810 @default.
• W2094837086 cites W1589297220 @default.
• W2094837086 cites W1592021885 @default.
• W2094837086 cites W1965173366 @default.
• W2094837086 cites W1965531638 @default.
• W2094837086 cites W1966524607 @default.
• W2094837086 cites W1967866958 @default.
• W2094837086 cites W1970431885 @default.
• W2094837086 cites W1971530571 @default.
• W2094837086 cites W1975277357 @default.
• W2094837086 cites W1976295398 @default.
• W2094837086 cites W1976633722 @default.
• W2094837086 cites W1978406914 @default.
• W2094837086 cites W1978518304 @default.
• W2094837086 cites W1986179131 @default.
• W2094837086 cites W1986512406 @default.
• W2094837086 cites W1988425997 @default.
• W2094837086 cites W1989525457 @default.
• W2094837086 cites W1993694367 @default.
• W2094837086 cites W1993916353 @default.
• W2094837086 cites W1994169350 @default.
• W2094837086 cites W1996675458 @default.
• W2094837086 cites W2000938936 @default.
• W2094837086 cites W2003925068 @default.
• W2094837086 cites W2003971548 @default.
• W2094837086 cites W2004311983 @default.
• W2094837086 cites W2007249806 @default.
• W2094837086 cites W2008072603 @default.
• W2094837086 cites W2008715871 @default.
• W2094837086 cites W2010045481 @default.
• W2094837086 cites W2012053348 @default.
• W2094837086 cites W2014875885 @default.
• W2094837086 cites W2015519364 @default.
• W2094837086 cites W2016396426 @default.
• W2094837086 cites W2017557952 @default.
• W2094837086 cites W2023950025 @default.
• W2094837086 cites W2024825463 @default.
• W2094837086 cites W2024996523 @default.
• W2094837086 cites W2034059961 @default.
• W2094837086 cites W2038167014 @default.
• W2094837086 cites W2038173255 @default.
• W2094837086 cites W2045086385 @default.
• W2094837086 cites W2046135777 @default.
• W2094837086 cites W2047884499 @default.
• W2094837086 cites W2048384924 @default.
• W2094837086 cites W2054208935 @default.
• W2094837086 cites W2055121057 @default.
• W2094837086 cites W2056530510 @default.
• W2094837086 cites W2058485582 @default.
• W2094837086 cites W2059848983 @default.
• W2094837086 cites W2070023783 @default.
• W2094837086 cites W2071178800 @default.
• W2094837086 cites W2071514329 @default.
• W2094837086 cites W2071555702 @default.
• W2094837086 cites W2071603995 @default.
• W2094837086 cites W2072594716 @default.
• W2094837086 cites W2073669361 @default.
• W2094837086 cites W2073936529 @default.
• W2094837086 cites W2076319176 @default.
• W2094837086 cites W2080125477 @default.
• W2094837086 cites W2082066478 @default.
• W2094837086 cites W2082979850 @default.
• W2094837086 cites W2087818316 @default.
• W2094837086 cites W2092663839 @default.
• W2094837086 cites W2094042239 @default.
• W2094837086 cites W2099907467 @default.
• W2094837086 cites W2104694670 @default.
• W2094837086 cites W2106048601 @default.
• W2094837086 cites W2110261435 @default.
• W2094837086 cites W2115905835 @default.
• W2094837086 cites W2116787167 @default.
• W2094837086 cites W2119337308 @default.
• W2094837086 cites W2123949630 @default.
• W2094837086 cites W2124052729 @default.
• W2094837086 cites W2125591199 @default.
• W2094837086 cites W2126166557 @default.
• W2094837086 cites W2131179850 @default.
• W2094837086 cites W2133959309 @default.
• W2094837086 cites W2136192296 @default.
• W2094837086 cites W2136605121 @default.
• W2094837086 cites W2137928263 @default.
• W2094837086 cites W2138187945 @default.
• W2094837086 cites W2138351931 @default.
• W2094837086 cites W2139466852 @default.

• next