Evidence map›Paper›PMID 12221136›Full record

ArticleMolecular biology of the cell2002

Proteasome regulates the delivery of LDL receptor-related protein into the degradation pathway.

Lora Melman, Hans J Geuze, Yonghe Li, Lynn M McCormick, Peter Van Kerkhof, Ger J Strous, Alan L Schwartz, Guojun Bu

Open access · greenAbstract read
In one paragraph

Article in Molecular biology of the cell, 2002. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.

0numbers the graph read from it
0cells of the map it votes in
20citing papers in PubMed
1.8field-weighted citation impact, top 17% 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

20 citing papers in PubMed, 42 citations in OpenAlex.

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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

8 authors at 2 institutions in 2 countries.

Lora MelmanDepartment of Pediatrics, Washington University School of Medicine, CB 8208, St. Louis Children's Hospital, Missouri 63110, USA.
Hans J Geuze
Yonghe Li
Lynn M McCormick
Peter Van Kerkhof
Ger J Strous
Alan L Schwartz
Guojun Bu
St. Louis Children's Hospital · USUtrecht University · NL

Funding

WASHINGTON UNIVERSITY ALZHEIMERS DISEASE RESEARCH CENTERP50AG005681 · NIA · WASHINGTON UNIVERSITY · PI MORRIS, JOHN · 1985 to 2019
$52.1M
BLOOD COAGULATION HOMESTASIS: REGULATION OF TFPIR01HL053280 · NHLBI · WASHINGTON UNIVERSITY · PI SCHWARTZ, ALAN L · 1995 to 2003
$988k
BIOGENESIS OF LIPOPROTEINS RECEPTORSR01DK061761 · NIDDK · WASHINGTON UNIVERSITY · PI BU, GUOJUN · 2001 to 2004
$953k
NEUROTROPHIN REGULATION OF LRP IN CNS NEURONSR01NS037525 · NINDS · WASHINGTON UNIVERSITY · PI BU, GUOJUN · 1998 to 2001
$452k
NHLBI NIH HHS HL53280NHLBI NIH HHS R01 HL053280NIA NIH HHS AG05681NIA NIH HHS P50 AG005681NIDDK NIH HHS DK61761NIDDK NIH HHS R01 DK061761NINDS NIH HHS NS37525
6 · The paper itself

Abstract

The low-density lipoprotein receptor (LDLR)-related protein (LRP) is a multiligand endocytic receptor that has broad cellular and physiological functions. Previous studies have shown that both tyrosine-based and di-leucine motifs within the LRP cytoplasmic tail are responsible for mediating its rapid endocytosis. Little is known, however, about the mechanism by which LRP is targeted for degradation. By examining both endogenous full-length and a minireceptor form of LRP, we found that proteasomal inhibitors, MG132 and lactacystin, prolong the cellular half-life of LRP. The presence of proteasomal inhibitors also significantly increased the level of LRP at the cell surface, suggesting that the delivery of LRP to the degradation pathway was blocked at a compartment from which recycling of the receptor to the cell surface still occurred. Immunoelectron microscopy analyses demonstrated a proteasomal inhibitor-dependent reduction in LRP minireceptor within both limiting membrane and internal vesicles of the multivesicular bodies, which are compartments that lead to receptor degradation. In contrast to the growth hormone receptor, we found that the initial endocytosis of LRP minireceptor does not require a functional ubiquitin-proteasome system. Finally, using truncated cytoplasmic mutants of LRP minireceptors, we found that a region of 19 amino acids within the LRP tail is required for proteasomal regulation. Taken together our results provide strong evidence that the cellular turnover of a cargo receptor, i.e., LRP, is regulated by the proteasomal system, suggesting a broader function of the proteasome in regulating the trafficking of receptors into the degradation pathway.

Indexed as

Amino Acid MotifsAnimalsBlotting, WesternCHO CellsCricetinaeCysteine EndopeptidasesCysteine Proteinase InhibitorsEndocytosisFlow CytometryHumansKineticsLeupeptinsLigandsLipoproteins, LDLLow Density Lipoprotein Receptor-Related Protein-1Microscopy, Fluorescencebenzyloxycarbonylleucyl-leucyl-leucine aldehydeCysteine EndopeptidasesCysteine Proteinase InhibitorsLeupeptinsLigandsLipoproteins, LDLLow Density Lipoprotein Receptor-Related Protein-1Multienzyme ComplexesProteasome Endopeptidase ComplexRecombinant Proteins

Identifiers

PMID12221136
PMCPMC124162
OpenAlexW2141430946

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.