ELIZA

return kwic search for revealed out of >500 occurrences
324965 occurrences (No.62 in the rank) during 5 years in the PubMed. [no cache] 500 found

408) We show that p53 is stabilized in the absence of pVHL and becomes hyperstabilized upon DNA damage, which we propose is because of a novel in vivo interaction revealed between human pVHL and a negative regulator of Mdm2, the programmed cell death 5 (PDCD5) protein.

--- ABSTRACT ---

PMID:24469044 DOI:10.1038/onc.2013.598

2015 Oncogene

* The von Hippel-Lindau tumor suppressor regulates programmed cell death 5-mediated degradation of Mdm2.

- Functional loss of the von Hippel-Lindau (VHL) tumor suppressor protein (pVHL), which is part of an E3-ubiquitin ligase complex, initiates most inherited and sporadic clear-cell renal cell carcinomas (ccRCC). Genetic inactivation of the TP53 gene in ccRCC is rare, suggesting that an alternate mechanism alleviates the selective pressure for TP53 mutations in ccRCC. Here we use a zebrafish model to describe the functional consequences of pVHL loss on the p53/Mdm2 pathway. We show that p53 is stabilized in the absence of pVHL and becomes hyperstabilized upon DNA damage, which we propose is because of a novel in vivo interaction revealed between human pVHL and a negative regulator of Mdm2, the programmed cell death 5 (PDCD5) protein. PDCD5 is normally localized at the plasma membrane and in the cytoplasm. However, upon hypoxia or loss of pVHL, PDCD5 relocalizes to the nucleus, an event that is coupled to the degradation of Mdm2. Despite the subsequent hyperstabilization and normal transcriptional activity of p53, we find that zebrafish vhl(-/-) cells are still as highly resistant to DNA damage-induced cell cycle arrest and apoptosis as human ccRCC cells. We suggest this is because of a marked increase in expression of birc5a, the zebrafish homolog of Survivin. Accordingly, when we knock down Survivin in human ccRCC cells we are able to restore caspase activity in response to DNA damage. Taken together, our study describes a new mechanism for p53 stabilization through PDCD5 upon hypoxia or pVHL loss, and reveals new clinical potential for the treatment of pathobiological disorders linked to hypoxic stress.

--- ABSTRACT END ---

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[frequency of next (right) word to revealed]

(1)193 that	(9)4 five	(17)2 common	(25)2 new
(2)61 a	(10)4 high	(18)2 distinct	(26)2 numerous
(3)21 the	(11)3 statistically	(19)2 enhanced	(27)2 right
(4)14 no	(12)3 that,	(20)2 evidence	(28)2 severe
(5)13 an	(13)3 three	(21)2 four	(29)2 significantly
(6)13 significant	(14)3 two	(22)2 higher
(7)7 by	(15)2 null	(23)2 in
(8)5 multiple	(16)2 as	(24)2 moderate

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--- WordNet output for revealed --- Overview of verb reveal The verb reveal has 3 senses (first 2 from tagged texts) 1. (34) uncover, bring out, unveil, reveal -- (make visible; "Summer brings out bright clothes"; "He brings out the best in her") 2. (17) unwrap, disclose, let on, bring out, reveal, discover, expose, divulge, break, give away, let out -- (make known to the public information that was previously known only to a few people or that was meant to be kept a secret; "The auction house would not disclose the price at which the van Gogh had sold"; "The actress won't reveal how old she is"; "bring out the truth"; "he broke the news to her"; "unwrap the evidence in the murder case") 3. reveal -- (disclose directly or through prophets; "God rarely reveal his plans for Mankind") --- WordNet end ---