Evidence map›Paper›PMID 30552871›Full record

ReviewBiochemical pharmacology2019

Darpp-32 and t-Darpp protein products of PPP1R1B: Old dogs with new tricks.

Arabo Avanes, Gal Lenz, Jamil Momand

Open access · greenAbstract readReview
In one paragraph

Review in Biochemical pharmacology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed
1.7field-weighted citation impact, top 12% 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

18 citing papers in PubMed, 31 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Review
  6. Metabolic hallmarks of trastuzumab resistance.Expert opinion on therapeutic targets · 2025
    Review
  7. Article
  8. Review
  9. Landscape of intrinsically disordered proteins in mental disorder diseases.Computational and structural biotechnology journal · 2024
    Article
  10. Article
  11. Article
  12. Oncogenic SRSF3 in health and diseases.International journal of biological sciences · 2023
    Review
  13. Article
  14. Article
  15. Article
  16. Article
  17. Article
  18. Article
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 2 institutions in 1 country.

Arabo AvanesDepartment of Chemistry and Biochemistry, California State University Los Angeles, CA, USA.
Gal LenzDepartment of Cancer Biology, City of Hope, CA 91010, USA. Electronic address: glenz@coh.org.
Jamil MomandDepartment of Chemistry and Biochemistry, California State University Los Angeles, CA, USA. Electronic address: jmomand@calstatela.edu.
California State University Los Angeles · USCity of Hope · US

Funding

Research Initiative for Scientific Enhancement (RISE)R25GM061331 · NIGMS · CALIFORNIA STATE UNIVERSITY LOS ANGELES · PI FOSTER, KRISHNA L · 2000 to 2021
$33.1M
Macromolecular Interactions of t-Darpp and Darpp-32R01GM105898 · NIGMS · CALIFORNIA STATE UNIVERSITY LOS ANGELES · PI MOMAND, JAMIL A, ZHOU, FEIMENG · 2014 to 2017
$1.3M
NIGMS NIH HHS R01 GM105898NIGMS NIH HHS R25 GM061331
6 · The paper itself

Abstract

The PPP1R1B gene is located on chromosome 17q12 (39,626,208-39,636,626[GRCh38/hg38]), which codes for multiple transcripts and two experimentally-documented proteins Darpp-32 and t-Darpp. Darpp-32 (Dopamine and cAMP Regulated Phosphoprotein), discovered in the early 1980s, is a protein whose phosphorylation is upregulated in response to cAMP in dopamine-responsive tissues in the brain. It's phosphorylation profile modulates its ability to bind and inhibit Protein Phosphatase 1 activity, which, in turn, controls the activity of hundreds of phosphorylated proteins. PPP1R1B knockout mice exhibit subtle learning defects. In 2002, the second protein product of PPP1R1B was discovered in gastric cancers: t-Darpp (truncated Darpp-32). The start codon of t-Darpp is amino acid residue 37 of Darpp-32 and it lacks the domain responsible for modulating Protein Phosphatase 1. Aside from gastric cancers, t-Darpp and/or Darpp-32 is overexpressed in tumor cells from breast, colon, esophagus, lung and prostate tissues. More than one research team has demonstrated that these proteins, through mechanisms that to date remain cloudy, activate AKT, a protein whose phosphorylation leads to cell survival and blocks apoptosis. Furthermore, in Her2 positive breast cancers (an aggressive form of breast cancer), t-Darpp/Darpp-32 overexpression causes resistance to the frequently-administered anti-Her2 drug, trastuzumab (Herceptin), likely through AKT activation. Here we briefly describe how Darpp-32 and t-Darpp were discovered and report on the current state of knowledge of their involvement in cancers. We present a case for the development of an anti-t-Darpp therapeutic agent and outline the unique challenges this endeavor will likely encounter.

Indexed as

AnimalsCell MovementDopamine and cAMP-Regulated Phosphoprotein 32Gene Expression RegulationHumansMice, TransgenicNeoplasmsNeuronsSignal TransductionXenograft Model Antitumor AssaysDopamine and cAMP-Regulated Phosphoprotein 32PPP1R1B protein, humanBreast cancerDopamineDrug resistanceGastric cancerPhosphoprotein

Identifiers

PMID30552871
PMCPMC6360145
OpenAlexW2904367878

What OpenQuestion holds

Textmetadata
LicenceTDM
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.