Evidence map›Paper›PMID 25016022›Full record

ArticleThe Journal of biological chemistry2014

Prolactin (PRL)-stimulated ubiquitination of ZnT2 mediates a transient increase in zinc secretion followed by ZnT2 degradation in mammary epithelial cells.

Young Ah Seo, Sooyeon Lee, Stephen R Hennigar, Shannon L Kelleher

Open access · hybridAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in The Journal of biological chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed, 1 pooled it
2.3field-weighted citation impact, top 13% 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

11 citing papers in PubMed, 1 synthesis or guideline pooled it, 18 citations in OpenAlex.

  1. Pooled it
  2. Role of zinc in health and disease.Clinical and experimental medicine · 2024
    Review
  3. Review
  4. ZnT2 is critical for lysosome acidification and biogenesis during mammary gland involution.American journal of physiology. Regulatory, integrative and comparative physiology · 2018
    Article
  5. Article
  6. Article
  7. Zinc-sensitive MRI contrast agent detects differential release of Zn(II) ions from the healthy vs. malignant mouse prostate.Proceedings of the National Academy of Sciences of the United States of America · 2016
    Article
  8. Article
  9. Article
  10. Article
  11. 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

4 authors at 3 institutions in 1 country.

Young Ah Seothe Department of Nutritional Sciences, Pennsylvania State University, University Park, Pennsylvania 16802, and the Departments of Genetics and Complex Diseases and Nutrition, Harvard School of Public Health, Boston, Massachusetts 02115.
Sooyeon Leethe Department of Nutritional Sciences, Pennsylvania State University, University Park, Pennsylvania 16802, and From the Departments of Cell and Molecular Physiology.
Stephen R Hennigarthe Department of Nutritional Sciences, Pennsylvania State University, University Park, Pennsylvania 16802, and.
Shannon L Kelleherthe Department of Nutritional Sciences, Pennsylvania State University, University Park, Pennsylvania 16802, and From the Departments of Cell and Molecular Physiology, Pharmacology, and Surgery, Penn State Hershey College of Medicine, Hershey, Pennsylvania 17033, slk39@psu.edu.
Pennsylvania State University · USHarvard University · USPenn State Milton S. Hershey Medical Center · US

Funding

Regulation of Cellular Zn Redistribution: A Role of ZnT2R01HD058614 · NICHD · PENNSYLVANIA STATE UNIVERSITY, THE · PI KELLEHER, SHANNON L · 2008 to 2012
$1.4M
NICHD NIH HHS R01 HD058614
6 · The paper itself

Abstract

The zinc transporter ZnT2 imports zinc into secretory vesicles and regulates zinc export from the mammary epithelial cell. Mutations in ZnT2 substantially impair zinc secretion into milk. The lactogenic hormone prolactin (PRL) transcriptionally increases ZnT2 expression through the Jak2/STAT5 signaling pathway, increasing zinc accumulation in secretory vesicles and zinc secretion. Herein, we report that PRL post-translationally stimulated ZnT2 ubiquitination, which altered ZnT2 trafficking and augmented vesicular zinc accumulation and secretion from mammary epithelial cells in a transient manner. Ubiquitination then down-regulated zinc secretion by stimulating degradation of ZnT2. Mutagenesis of two N-terminal lysine residues (K4R and K6R) inhibited ZnT2 ubiquitination, vesicular zinc accumulation and secretion, and protein degradation. These findings establish that PRL post-translationally regulates ZnT2-mediated zinc secretion in a multifactorial manner, first by enhancing zinc accumulation in vesicles to transiently enhance zinc secretion and then by activating ubiquitin-dependent ZnT2 degradation. This provides insight into novel mechanisms through which ZnT2 and zinc transport is tightly regulated in mammary epithelial cells.

Indexed as

AnimalsBase SequenceCation Transport ProteinsCell LineEpithelial CellsFemaleImmunoprecipitationLysineMammary Glands, AnimalMiceProlactinProtein Processing, Post-TranslationalRNA, Small InterferingUbiquitinationCation Transport ProteinsLysineProlactinRNA, Small InterferingZnt2 protein, mouseMammary GlandProlactinProtein DegradationSecretionUbiquitinationZinc TransporterZnT2

Identifiers

PMID25016022
PMCPMC4156067
OpenAlexW2051634390

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.