Evidence map›Paper›PMID 32283065›Full record

ArticleExperimental cell research2020

Dissecting the novel partners of nuclear c-Raf and its role in all-trans retinoic acid (ATRA)-induced myeloblastic leukemia cells differentiation.

Asif Rashid, Rui Wang, Liang Zhang, Jianbo Yue, Mengsu Yang, Andrew Yen

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

Article in Experimental cell research, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
0.2field-weighted citation impact, top 51% 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

4 citing papers in PubMed, 4 citations in OpenAlex.

  1. SMARCD1 and Its Functional Relevance in SWI/SNF and Cancer.International journal of molecular sciences · 2026
    Review
  2. Article
  3. Review
  4. 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

6 authors at 3 institutions in 3 countries.

Asif RashidDepartment of Biomedical Sciences, City University of Hong Kong, Kowloon, Hong Kong SAR, China; Department of Biomedical Sciences, Cornell University, Ithaca, NY 14853, USA; Department of Pathology, The University of Hong Kong, Queen Mary Hospital, Pokfulam, Hong Kong SAR, China.
Rui WangDepartment of Biomedical Sciences, City University of Hong Kong, Kowloon, Hong Kong SAR, China; Key Laboratory of Biochip Technology, Biotech and Health Centre, Shenzhen Research Institute of City University of Hong Kong, Shenzhen, 518057, China.
Liang ZhangDepartment of Biomedical Sciences, City University of Hong Kong, Kowloon, Hong Kong SAR, China; Key Laboratory of Biochip Technology, Biotech and Health Centre, Shenzhen Research Institute of City University of Hong Kong, Shenzhen, 518057, China.
Jianbo YueDepartment of Biomedical Sciences, City University of Hong Kong, Kowloon, Hong Kong SAR, China.
Mengsu YangDepartment of Biomedical Sciences, City University of Hong Kong, Kowloon, Hong Kong SAR, China. Electronic address: bhmyang@cityu.edu.hk.
Andrew YenDepartment of Biomedical Sciences, Cornell University, Ithaca, NY 14853, USA. Electronic address: ay13@cornell.edu.
City University of Hong Kong · HKCornell University · USQueen Mary Hospital · CN

Funding

Mechanism of Action of Retinoic Acid Using CD38R01CA152870 · NCI · CORNELL UNIVERSITY · PI HAO, QUAN, LIN, HENING · 2011 to 2015
$1.6M
NCI NIH HHS R01 CA152870
6 · The paper itself

Abstract

All-trans retinoic acid (ATRA) is an anti-cancer differentiation therapy agent effective for acute promyelocytic leukemia (APL) but not acute myeloid leukemia (AML) in general. Using the HL-60 human non-APL AML model where ATRA causes nuclear enrichment of c-Raf that drives differentiation and G1/G0 cell cycle arrest, we now observe that c-Raf in the nucleus showed novel interactions with several prominent regulators of the cell cycle and cell differentiation. One is cyclin-dependent kinase 2 (Cdk2). ATRA treatment caused c-Raf to dissociate from Cdk2. This was associated with enhanced binding of Cdk2 with retinoic acid receptor α (RARα). Consistent with this novel Raf/CDK2/RARα axis contributing to differentiation, CD38 expression per cell, which is transcriptionally regulated by a retinoic acid response element (RARE), is enhanced. The RB tumor suppressor, a fundamental regulator of G1 cell cycle progression or arrest, was also targeted by c-Raf in the nucleus. RB and specifically the S608 phosphorylated form (pS608RB) complexed with c-Raf. ATRA treatment induced S608RB-hypophosphorylation associated with G1/G0 cell cycle arrest and release of c-Raf from RB. We also found that nuclear c-Raf interacted with SMARCD1, a pioneering component of the SWI/SNF chromatin remodeling complex. ATRA treatment diminished the amount of this protein bound to c-Raf. The data suggest that ATRA treatment to HL-60 human cells re-directed c-Raf from its historically pro-proliferation functions in the cytoplasm to pro-differentiation functions in the nucleus.

Indexed as

Antineoplastic AgentsCell DifferentiationCell DivisionG1 Phase Cell Cycle CheckpointsHL-60 CellsHumansLeukemia, Promyelocytic, AcutePhosphorylationProto-Oncogene Proteins c-rafRetinoic Acid Receptor alphaTretinoinAntineoplastic AgentsProto-Oncogene Proteins c-rafRaf1 protein, humanRetinoic Acid Receptor alphaTretinoinAPLATRACyclin-dependent kinase 2RBSMARCD1

Identifiers

PMID32283065
PMCPMC10656057
OpenAlexW3015251539

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.