↓ Skip to main content

Leucine-Rich Repeat Kinase 2 (LRRK2) phosphorylates p53 and induces p21WAF1/CIP1 expression

Overview of attention for article published in Molecular Brain, September 2015
Altmetric Badge

About this Attention Score

  • In the top 25% of all research outputs scored by Altmetric
  • High Attention Score compared to outputs of the same age (85th percentile)
  • High Attention Score compared to outputs of the same age and source (90th percentile)

Mentioned by

news
1 news outlet
twitter
3 X users

Citations

dimensions_citation
51 Dimensions

Readers on

mendeley
43 Mendeley
citeulike
1 CiteULike
You are seeing a free-to-access but limited selection of the activity Altmetric has collected about this research output. Click here to find out more.
Title
Leucine-Rich Repeat Kinase 2 (LRRK2) phosphorylates p53 and induces p21WAF1/CIP1 expression
Published in
Molecular Brain, September 2015
DOI 10.1186/s13041-015-0145-7
Pubmed ID
Authors

Dong Hwan Ho, Hyejung Kim, Jisun Kim, Hyuna Sim, Hyunjun Ahn, Janghwan Kim, Hyemyung Seo, Kwang Chul Chung, Bum-Joon Park, Ilhong Son, Wongi Seol

Abstract

Leucine-rich repeat kinase 2 (LRRK2) is a gene in which a mutation causes Parkinson's disease (PD), and p53 is a prototype tumor suppressor. In addition, activation of p53 in patient with PD has been reported by several studies. Because phosphorylation of p53 is critical for regulating its activity and LRRK2 is a kinase, we tested whether p53 is phosphorylated by LRRK2. LRRK2 phosphorylates threonine (Thr) at TXR sites in an in vitro kinase assay, and the T304 and T377 were identified as putative phosphorylated residues. An increase of phospho-Thr in the p53 TXR motif was confirmed in the cells overexpressing G2019S, and human induced pluripotent stem (iPS) cells of a G2019S carrier. Interactions between LRRK2 and p53 were confirmed by co-immunoprecipitation of lysates of differentiated SH-SY5Y cells. LRRK2 mediated p53 phosphorylation translocalizes p53 predominantly to nucleus and increases p21(WAF1/CIP1) expression in SH-SY5Y cells based on reverse transcription-polymerase chain reaction and Western blot assay results. The luciferase assay using the p21(WAF1/CIP1) promoter-reporter also confirmed that LRRK2 kinase activity increases p21 expression. Exogenous expression of G2019S and the phosphomimetic p53 T304/377D mutants increased expression of p21(WAF1/CIP1) and cleaved PARP, and cytotoxicity in the same cells. We also observed increase of p21 expression in rat primary neuron cells after transient expression of p53 T304/377D mutants and the mid-brain lysates of the G2019S transgenic mice. p53 is a LRRK2 kinase substrate. Phosphorylation of p53 by LRRK2 induces p21(WAF1/CIP1) expression and apoptosis in differentiated SH-SY5Y cells and rat primary neurons.

X Demographics

X Demographics

The data shown below were collected from the profiles of 3 X users who shared this research output. Click here to find out more about how the information was compiled.
Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 43 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
United States 1 2%
Unknown 42 98%

Demographic breakdown

Readers by professional status Count As %
Researcher 8 19%
Student > Master 8 19%
Student > Bachelor 6 14%
Student > Ph. D. Student 6 14%
Student > Doctoral Student 3 7%
Other 6 14%
Unknown 6 14%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 12 28%
Agricultural and Biological Sciences 10 23%
Medicine and Dentistry 6 14%
Neuroscience 6 14%
Business, Management and Accounting 1 2%
Other 2 5%
Unknown 6 14%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 11. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 12 February 2016.
All research outputs
#2,784,382
of 23,339,727 outputs
Outputs from Molecular Brain
#118
of 1,135 outputs
Outputs of similar age
#38,828
of 274,095 outputs
Outputs of similar age from Molecular Brain
#3
of 21 outputs
Altmetric has tracked 23,339,727 research outputs across all sources so far. Compared to these this one has done well and is in the 87th percentile: it's in the top 25% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 1,135 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 7.0. This one has done well, scoring higher than 89% of its peers.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 274,095 tracked outputs that were published within six weeks on either side of this one in any source. This one has done well, scoring higher than 85% of its contemporaries.
We're also able to compare this research output to 21 others from the same source and published within six weeks on either side of this one. This one has done particularly well, scoring higher than 90% of its contemporaries.