SLFN14 functions as a P-TEFb inhibitor to modulate the transcription of HIV-1 and cellular genes

The <i>Schlafen</i> (<i>SLFN</i>) gene family encodes different growth regulatory factors known to participate in cell growth, differentiation, tumorigenesis, and the immune response against virus infection. However, the molecular mechanisms underlying their functions remain largely incomplete. In this study, we report that the SLFN family member SLFN14 has potent anti-HIV-1 activity. Specifically, SLFN14 binds to the positive transcription elongation factor b (P-TEFb), thereby preventing HIV-1 Tat-mediated recruitment of P-TEFb to the HIV-1 promoter and causing an arrest of viral transcription. Furthermore, this P-TEFb-targeted inhibiting activity also allows SLFN14 to regulate the transcription of a subset of cellular genes. Thus, our data identify SLFN14 as an inhibitor of the important transcription elongation factor P-TEFb complex, which unveils the crucial role of SLFN14 in both cellular antiviral defense and other important cellular processes that rely on the function of this complex.

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Publication Details

Journal
Science Advances
Published
2025-12-17
DOI
https://doi.org/10.1126/sciadv.adt7982
Citations
1
Primary Topic
PARP inhibition in cancer therapy
Type
article
Field-Weighted Citation Impact
1.05
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article

SLFN14 functions as a P-TEFb inhibitor to modulate the transcription of HIV-1 and cellular genes

Jing Wang, Quanjie Li, Dongrong Yi, Shan Cen et al.
1 citations
Science Advances
PARP inhibition in cancer therapy
1.05
article

SLFN14 functions as a P-TEFb inhibitor to modulate the transcription of HIV-1 and cellular genes

Jing Wang, Quanjie Li, Dongrong Yi, Shan Cen, Saisai Guo, Zhenlong Liu, Rui Zhou, Zhen Wang, Yongxin Zhang, Ling Ma, Xiaoyu Li, Jiwei Ding, Xinlu Wang, Shumin Chen, Jianyuan Zhao
article en
1 citations

Abstract

The <i>Schlafen</i> (<i>SLFN</i>) gene family encodes different growth regulatory factors known to participate in cell growth, differentiation, tumorigenesis, and the immune response against virus infection. However, the molecular mechanisms underlying their functions remain largely incomplete. In this study, we report that the SLFN family member SLFN14 has potent anti-HIV-1 activity. Specifically, SLFN14 binds to the positive transcription elongation factor b (P-TEFb), thereby preventing HIV-1 Tat-mediated recruitment of P-TEFb to the HIV-1 promoter and causing an arrest of viral transcription. Furthermore, this P-TEFb-targeted inhibiting activity also allows SLFN14 to regulate the transcription of a subset of cellular genes. Thus, our data identify SLFN14 as an inhibitor of the important transcription elongation factor P-TEFb complex, which unveils the crucial role of SLFN14 in both cellular antiviral defense and other important cellular processes that rely on the function of this complex.

Science AdvancesVol. 11(51)
Qingdao University (CN), Chinese Academy of Medical Sciences & Peking Union Medical College (CN), Jewish General Hospital (CA), Institute of Biophysics (CN), Affiliated Hospital of Qingdao University (CN)
Openalex Percentile: Top 15%
PARP inhibition in cancer therapy
1.05
DOIOpen Access PDFOpenAlex
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