ELIZA

return kwic search for growth out of >500 occurrences
309169 occurrences (No.70 in the rank) during 5 years in the PubMed. [cache]

267) 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.

--- 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.

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[frequency of next (right) word to growth]

(1)69 and	(12)5 at	(25)3 models	(36)2 model
(2)48 factor	(13)4 but	(26)3 or	(37)2 modeling
(3)48 of	(14)4 during	(27)3 traits	(38)2 outcomes
(4)41 null	(15)4 factor,	(28)3 trajectories	(39)2 phase
(5)32 in	(17)4 patterns	(29)2 among	(40)2 properties
(6)25 factors	(18)4 plate	(30)2 are	(41)2 responses
(7)9 inhibition	(19)4 response	(31)2 as	(42)2 restriction
(8)8 rate	(20)4 was	(32)2 dynamics	(43)2 stunting
(9)6 factors,	(21)3 cone	(33)2 effects	(44)2 to
(10)6 rates	(22)3 curve	(34)2 forest	(45)2 velocities
(11)5 arrest	(23)3 factor-C	(35)2 hormone	(46)2 were

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--- WordNet output for growth --- =>茂み, 成長, 増加, 発展, 栽培, 腫よう, 成長物 Overview of noun growth The noun growth has 7 senses (first 5 from tagged texts) 1. (37) growth, growing, maturation, development, ontogeny, ontogenesis -- ((biology) the process of an individual organism growing organically; a purely biological unfolding of events involved in an organism changing gradually from a simple to a more complex level; "he proposed an indicator of osseous development in children") 2. (20) growth -- (a progression from simpler to more complex forms; "the growth of culture") 3. (3) increase, increment, growth -- (a process of becoming larger or longer or more numerous or more important; "the increase in unemployment"; "the growth of population") 4. (3) growth -- (vegetation that has grown; "a growth of trees"; "the only growth was some salt grass") 5. (1) emergence, outgrowth, growth -- (the gradual beginning or coming forth; "figurines presage the emergence of sculpture in Greece") 6. growth -- ((pathology) an abnormal proliferation of tissue (as in a tumor)) 7. growth -- (something grown or growing; "a growth of hair") --- WordNet end ---