IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v16y2025i1d10.1038_s41467-025-56532-3.html
   My bibliography  Save this article

p85β acts as a transcription cofactor and cooperates with BCLAF1 in the nucleus

Author

Listed:
  • Panpan Wang

    (The University of Hong Kong)

  • Victor CY Mak

    (The University of Hong Kong)

  • Ling Rao

    (The University of Hong Kong)

  • Qiuqiu Wu

    (The University of Hong Kong)

  • Yuan Zhou

    (The University of Hong Kong)

  • Rakesh Sharma

    (The University of Hong Kong)

  • S. Chul Kwon

    (The University of Hong Kong)

  • Lydia WT Cheung

    (The University of Hong Kong)

Abstract

p85β is a regulatory subunit of the phosphoinositide 3-kinase (PI3K). Emerging evidence suggests that p85β goes beyond its role in the PI3K and is functional in the nucleus. In this study, we discover that nuclear p85β is enriched at gene loci and regulates gene transcription and that this regulatory role contributes to the oncogenic potential of nuclear p85β. A multi-omics approach reveals the physical interaction and functional cooperativity between nuclear p85β and a transcription factor BCLAF1. We observe genome-wide co-occupancy of p85β and BCLAF1 at gene targets associated with transcriptional responses. Intriguingly, the targetome includes BCLAF1 of which transcription is activated by p85β and BCLAF1, indicating a positive autoregulation. While BCLAF1 recruits p85β to BCLAF1 loci, p85β facilitates the assembly of BCLAF1, the scaffold protein TRIM28 and the zinc finger transcription factor ZNF263, which together act in concert to activate BCLAF1 transcription. Collectively, this study provides functional evidence and mechanistic basis to support a role of nuclear p85β in modulating gene transcription.

Suggested Citation

  • Panpan Wang & Victor CY Mak & Ling Rao & Qiuqiu Wu & Yuan Zhou & Rakesh Sharma & S. Chul Kwon & Lydia WT Cheung, 2025. "p85β acts as a transcription cofactor and cooperates with BCLAF1 in the nucleus," Nature Communications, Nature, vol. 16(1), pages 1-20, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-56532-3
    DOI: 10.1038/s41467-025-56532-3
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-025-56532-3
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-025-56532-3?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    References listed on IDEAS

    as
    1. Xuexia Zhou & Xuebing Li & Yuanming Cheng & Wenwu Wu & Zhiqin Xie & Qiulei Xi & Jun Han & Guohao Wu & Jing Fang & Ying Feng, 2014. "BCLAF1 and its splicing regulator SRSF10 regulate the tumorigenic potential of colon cancer cells," Nature Communications, Nature, vol. 5(1), pages 1-11, December.
    2. Thati Madhusudhan & Hongjie Wang & Wei Dong & Sanchita Ghosh & Fabian Bock & Veera Raghavan Thangapandi & Satish Ranjan & Juliane Wolter & Shrey Kohli & Khurrum Shahzad & Florian Heidel & Martin Krueg, 2015. "Defective podocyte insulin signalling through p85-XBP1 promotes ATF6-dependent maladaptive ER-stress response in diabetic nephropathy," Nature Communications, Nature, vol. 6(1), pages 1-15, May.
    Full references (including those not matched with items on IDEAS)

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.
    1. Yujun Hao & Baoyu He & Liping Wu & Yamu Li & Chao Wang & Ting Wang & Longci Sun & Yanhua Zhang & Yangyang Zhan & Yiqing Zhao & Sanford Markowitz & Martina Veigl & Ronald A. Conlon & Zhenghe Wang, 2022. "Nuclear translocation of p85β promotes tumorigenesis of PIK3CA helical domain mutant cancer," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    2. Abigail C. Lay & Van Du T. Tran & Viji Nair & Virginie Betin & Jennifer A. Hurcombe & Alexandra F. Barrington & Robert JP Pope & Frédéric Burdet & Florence Mehl & Dmytro Kryvokhyzha & Abrar Ahmad & Ma, 2024. "Profiling of insulin-resistant kidney models and human biopsies reveals common and cell-type-specific mechanisms underpinning Diabetic Kidney Disease," Nature Communications, Nature, vol. 15(1), pages 1-19, December.
    3. Ji-Hee Kim & Kyu-Hee Hwang & Bao T. N. Dang & Minseob Eom & In Deok Kong & Yousang Gwack & Seyoung Yu & Heon Yung Gee & Lutz Birnbaumer & Kyu-Sang Park & Seung-Kuy Cha, 2021. "Insulin-activated store-operated Ca2+ entry via Orai1 induces podocyte actin remodeling and causes proteinuria," Nature Communications, Nature, vol. 12(1), pages 1-13, December.
    4. Cunjie Chang & Muthukumar Rajasekaran & Yiting Qiao & Heng Dong & Yu Wang & Hongping Xia & Amudha Deivasigamani & Minjie Wu & Karthik Sekar & Hengjun Gao & Mengqing Sun & Yuqin Niu & Qian Li & Lin Tao, 2022. "The aberrant upregulation of exon 10-inclusive SREK1 through SRSF10 acts as an oncogenic driver in human hepatocellular carcinoma," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
    5. Moh’d Mohanad Al-Dabet & Khurrum Shahzad & Ahmed Elwakiel & Alba Sulaj & Stefan Kopf & Fabian Bock & Ihsan Gadi & Silke Zimmermann & Rajiv Rana & Shruthi Krishnan & Dheerendra Gupta & Jayakumar Manoha, 2022. "Reversal of the renal hyperglycemic memory in diabetic kidney disease by targeting sustained tubular p21 expression," Nature Communications, Nature, vol. 13(1), pages 1-17, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-56532-3. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.