ELIZA

return kwic search for identified out of >500 occurrences
324223 occurrences (No.64 in the rank) during 5 years in the PubMed. [cache]

259) NEDD4-1 was identified from Jurkat cytosolic fractions using an enzyme-dead Mdm2 mutant protein as a substrate for in vitro E3 ligase assays.

--- ABSTRACT ---

PMID:24413081 DOI:10.1038/onc.2013.557

2015 Oncogene

* Regulation of Mdm2 protein stability and the p53 response by NEDD4-1 E3 ligase.

- Mdm2 is a critical negative regulator of the tumor suppressor protein p53. Mdm2 is an E3 ligase whose overexpression leads to functional inactivation of p53. Mdm2 protein stability is regulated by several mechanisms including RING (Really Interesting New Gene) domain-mediated autoubiquitination. Here we report biochemical identification of NEDD4-1 as an E3 ligase for Mdm2 that contributes to the regulation of Mdm2 protein stability in cells. NEDD4-1 was identified from Jurkat cytosolic fractions using an enzyme-dead Mdm2 mutant protein as a substrate for in vitro E3 ligase assays. We show that lysates from Nedd4-1 knockout (KO) mouse embryonic fibroblasts (MEFs) have significantly diminished E3 ligase activity toward Mdm2 compared with lysates from wild-type (WT) MEFs. Recombinant NEDD4-1 promotes Mdm2 ubiquitination in vitro in a concentration- and time-dependent manner. In cells, NEDD4-1 physically interacts with Mdm2 via the RING domain of Mdm2. Overexpression of NEDD4-1, but not an enzyme-dead NEDD4-1CS mutant, increases ubiquitination of Mdm2. NEDD4-1 catalyzes the formation of K63-type polyubiquitin chains on Mdm2 that are distinct from K48-type polyubiquitination chains mediated by the Mdm2/MdmX complex. Importantly, K63-type polyubiquitination by NEDD4-1 competes with K48-type polyubiquitination on Mdm2 in cells. As a result, NEDD4-1-mediated ubiquitination stabilizes Mdm2. NEDD4-1 knockdown reduces the t1/2 (half-life) of endogenous Mdm2 from 20 to 12 min in U2OS cells. Nedd4-1 KO MEFs manifest increased p53 levels and activity, a more robust DNA damage response and increased G1 arrest compared with WT MEFs. Similarly, NEDD4-1 knockdown in WT-p53-bearing cells increases basal p53 levels and activity in an Mdm2-dependent manner, causes stronger p53 responses to DNA damage and results in p53-dependent growth inhibition compared with corresponding NEDD4-1-proficient control cells. This study identifies NEDD4-1 as a novel component of the p53/Mdm2 regulatory feedback loop that controls p53 activity during stress responses.

--- ABSTRACT END ---

[
right
kwic]

[frequency of next (right) word to identified]

(1)62 as	(11)7 based	(21)3 an	(31)2 differences
(2)54 in	(12)7 on	(22)3 during	(32)2 five
(3)38 null	(13)6 with	(23)3 factors	(33)2 for
(4)24 by	(14)5 between	(24)3 several	(34)2 regulation
(5)21 and	(15)5 to	(25)3 three	(35)2 their
(6)19 the	(16)5 two	(26)2 14	(36)2 themes
(7)18 a	(17)4 four	(27)2 4	(37)2 through
(8)12 using	(18)4 including	(28)2 are
(9)10 that	(19)4 which	(29)2 at
(10)8 from	(20)3 along	(30)2 but

add keyword

--- WordNet output for identified --- =>確認飛行物体;略:IFO Overview of verb identify The verb identify has 6 senses (first 6 from tagged texts) 1. (32) identify, place -- (recognize as being; establish the identity of someone or something; "She identified the man on the 'wanted' poster") 2. (7) name, identify -- (give the name or identifying characteristics of; refer to by name or some other identifying characteristic property; "Many senators were named in connection with the scandal"; "The almanac identifies the auspicious months") 3. (6) identify -- (consider (oneself) as similar to somebody else; "He identified with the refugees") 4. (4) identify -- (conceive of as united or associated; "Sex activity is closely identified with the hypothalamus") 5. (2) identify, discover, key, key out, distinguish, describe, name -- (identify as in botany or biology, for example) 6. (2) identify -- (consider to be equal or the same; "He identified his brother as one of the fugitives") Overview of adj identified The adj identified has 1 sense (first 1 from tagged texts) 1. (1) identified -- (having the identity known or established; "the identified bodies were released for burial") --- WordNet end ---