Evidence map›Paper›PMID 12190111›Full record

ArticleMolecular and cellular biochemistry2002

Activation of Raf-1/MEK-1/2/p42/44(MAPK) cascade alone is sufficient to uncouple LDL receptor expression from cell growth.

Gurpreet S Kapoor, Brett A Atkins, Kamal D Mehta

Abstract read
PubMed Publisher
In one paragraph

Article in Molecular and cellular biochemistry, 2002. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed, 1 pooled it
0.8field-weighted citation impact, top 31% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

9 citing papers in PubMed, 1 synthesis or guideline pooled it, 20 citations in OpenAlex.

  1. Pooled it
  2. PKCβ: Expanding role in hepatic adaptation of cholesterol homeostasis to dietary fat/cholesterol.American journal of physiology. Gastrointestinal and liver physiology · 2017
    Review
  3. Article
  4. Article
  5. Article
  6. Article
  7. Human low-density lipoprotein receptor gene and its regulation.Journal of molecular medicine (Berlin, Germany) · 2006
    Review
  8. Myc-interacting protein 1 target gene profile: a link to microtubules, extracellular signal-regulated kinase, and cell growth.Proceedings of the National Academy of Sciences of the United States of America · 2004
    Article
  9. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

3 authors at 1 institution in 1 country.

Gurpreet S KapoorDepartment of Molecular and Cellular Biochemistry, The Ohio State University College of Medicine, Columbus 43210, USA.
Brett A Atkins
Kamal D Mehta
The Ohio State University · US

Funding

Mechanisms of p42/44MAPK-induced LDL receptor expressionR01HL065540 · NHLBI · OHIO STATE UNIVERSITY · PI MEHTA, KAMAL D · 2001 to 2004
$1.1M
MECHANISM OF STEROL REGULATION OF LDL RECEPTOR GENER29HL051592 · NHLBI · UNIVERSITY OF ARKANSAS MED SCIS LTL ROCK · PI MEHTA, KAMAL D · 1994 to 1998
–
NHLBI NIH HHS R01 HL-65540-01A1
6 · The paper itself

Abstract

Our previous observation that induction of low density lipoprotein (LDL) receptor expression by a variety of extracellular signals is blocked by PD98059, a specific mitogen-activated protein kinase kinase inhibitor, led to the suggestion that the growth-responsive p42/44(MAPK) cascade plays a critical role in regulating LDL receptor transcription. To analyze the specific contribution of the p42/44(MAPK) cascade in regulating cell growth and LDL receptor induction, we established a HepG2-derived cell line that stably expresses an inducible form of oncogenic human Raf-1 kinase. Using this system, we provide direct evidence that specific activation of this cascade alone is not only required but is sufficient to fully induce LDL receptor expression. Interestingly, degree of p42/44(MAPK) activation determines the extent of LDL receptor induction. However, activation of p42/44(MAPK) in the above cells led to the inhibition of DNA synthesis, caused growth arrest, decrease in cyclin A and upregulation of p21(Cip) expression in a time-dependent manner. These results suggest that each of these two processes can be regulated independently of each other in response to p42/44(MAPK) activation. Thus, extent of p42/44(MAPK) activation may be important in transducing divergent cellular responses in human cells with implications for altered signaling resulting in hypercholesterolemia.

Indexed as

Blotting, NorthernCell CycleCell DivisionCurcuminCyclin ADNADose-Response Relationship, DrugEnzyme ActivationEnzyme InhibitorsFlavonoidsHumansHypercholesterolemiaImmunoblottingLuciferasesMAP Kinase Kinase 1MAP Kinase Kinase 22-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-oneCurcuminCyclin ADNAEnzyme InhibitorsFlavonoidsLuciferasesMAP2K1 protein, humanMAP2K2 protein, humanMAP Kinase Kinase 1MAP Kinase Kinase 2Mitogen-Activated Protein Kinase 1Mitogen-Activated Protein Kinase 3Mitogen-Activated Protein Kinase KinasesMitogen-Activated Protein KinasesProtein Serine-Threonine KinasesProtein-Tyrosine KinasesProto-Oncogene Proteins c-rafReceptors, LDLStaurosporine

Identifiers

PMID12190111
OpenAlexW47796

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.