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Cited by 54Hedgehog Signaling Pathway StudiesHistone Deacetylase Inhibitors ResearchCell death mechanisms and regulation

RETRACTED ARTICLE: Histone acetyltransferase PCAF accelerates apoptosis by repressing a GLI1/BCL2/BAX axis in hepatocellular carcinoma

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Gai, X, Tu, K, Li, C, Lu, Z, Roberts, L R, Zheng, X·2015·Cell Death & Disease
DOI 10.1038/cddis.2015.76PMC PMC4650545
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Abstract

P300/CBP-associated factor (PCAF), a histone acetyltransferase (HAT), has been found to regulate numerous cell signaling pathways controlling cell fate by acetylating both histone and non-histone proteins. We previously reported that PCAF upregulates cell apoptosis by inactivating Serine/Threonine Protein Kinase 1 (AKT1) signaling and consequently inhibits hepatocellular carcinoma (HCC) cell growth. Here, we show that PCAF can directly acetylate cytoplasmic GLI1 protein at lysine 518, preventing its nuclear translocation and promoter occupancy, and consequently suppressing Hedgehog (Hh) signaling in HCC. Further, our results show that GLI1 can increase Bcl-2 expression and downregulate BAX. Interestingly, forced expression of PCAF reduced Bcl-2 expression, upregulated BAX and repressed cell apoptosis. Further, we provide evidence that knockdown of GLI1 abrogates the inhibitory effect of PCAF on the growth of HCC in vitro. PCAF was also found to sensitize HCC cells to 5-fluorouracil (5-FU) treatment by regulating GLI1/Bcl-2/BAX axis-dependent apoptosis. In vivo experiments also confirmed the regulatory effect of PCAF on the GLI1/Bcl-2/BAX axis and its synergistic antitumor effects with 5-FU. Gene expression microarray studies showed that PCAF was downregulated in HCC tissues compared with adjacent liver tissues and that PCAF expression was significantly associated with longer overall survival and recurrence-free survival after surgery. Together, these results show that PCAF can induce cell apoptosis by modulating a GLI1/Bcl-2/BAX axis that in turn suppresses HCC progression, and suggest that 5-FU may exert a stronger anti-tumor effect in patients with PCAF expression in HCC tumors.

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  • Activated Gli1 translocates to the nucleus and activates transcription of genes that promote cell survival and proliferation, such as Gli1, Ptch1, and Bcl-2.

    “Activated Gli1 translocates to the nucleus and activates the transcription of genes that promote cell survival and proliferation, such as Gli1, Ptch1, and Bcl‐2 [31].”

    From Saikosaponin b1 Attenuates Liver Fibrosis by Blocking STAT3/Gli1 Interaction and Inducing Gli1 Degradation (2025) · cites this paper as [31]

    The Results section reports GLI1 nuclear translocation, occupancy of the PTCH1 promoter, and changes in GLI1 and PTCH1 expression. The Abstract says GLI1 upregulates its own expression, while the Discussion links GLI1 to Bcl-2 regulation and resistance to apoptosis. Our copy does not establish that all three named genes promote both cell survival and proliferation. (LLM, conf=0.82)

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Research works printed but not linked: 31

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Cited by

Sorted by citations

Authors
Gai, X., Tu, K., Li, C., Lu, Z., Roberts, L. R., & Zheng, X.
Affiliations
  • First Affiliated Hospital of Xi'an Jiaotong University (CN)
  • Mayo Clinic (US)
Corresponding author
Zheng, X
ORCID
Venue
Cell Death & Disease
Publisher
Springer Science and Business Media LLC
Published
2015-04-09
Volume
6
Issue
4
Pages
e1712-e1712
ISSN
2041-4889 (ISSN-L)
DOI
10.1038/cddis.2015.76
PMC
PMC4650545
OpenAlex
W2019789399
Cited by
54
References
0
Citations by year
2025: 4 · 2024: 3 · 2023: 6 · 2022: 4 · 2021: 6 · 2020: 4 · 2019: 5 · 2018: 7 · 2017: 7 · 2016: 7 · 2015: 1
FWCI
3.19
Type
journal article
Language
en
Status
Retracted
Update notices
retraction (2026-10-08)
Open access
Licence
Locations
  • Cell Death and Disease (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
Funders
  • Key Science and Technology Program of Shaanxi Province (2014K11-01-01-21)
  • National Cancer Institute
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Hedgehog Signaling Pathway Studies
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Histone Deacetylase Inhibitors Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
Keywords
PCAF, histone acetyltransferase, hepatocellular carcinoma, apoptosis, Gli1, Bcl-2, Bax, Hedgehog signaling, protein acetylation, 5-fluorouracil, chemosensitization, tumor recurrence, overall survival
MeSH terms
Zinc Finger Protein GLI1, p300-CBP-Associated Factor, Acetylation, Cytoplasm, Carcinoma, Hepatocellular, Humans, Liver Neoplasms, Transcription Factors, Signal Transduction, Down-Regulation, Apoptosis, Proto-Oncogene Proteins c-bcl-2, Cell Line, Tumor, p300-CBP Transcription Factors, bcl-2-Associated X Protein

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