Summary of project PR002173
This data is available at the NIH Common Fund's National Metabolomics Data Repository (NMDR) website, the Metabolomics Workbench, https://www.metabolomicsworkbench.org, where it has been assigned Project ID PR002173. The data can be accessed directly via it's Project DOI: 10.21228/M8R23J This work is supported by NIH grant, U2C- DK119886.
See: https://www.metabolomicsworkbench.org/about/howtocite.php
| Project ID: | PR002173 |
| Project DOI: | doi: 10.21228/M8R23J |
| Project Title: | Micropeptide hSPAR, a glutamine regulator, suppresses tumor growth via TRIM21-P27KIP1-mTOR pathway |
| Project Summary: | The mammalian target of rapamycin (mTOR) plays pivotal roles in cancer growth control upon amino acid response. Recently, cyclin-dependent kinase (CDK) inhibitor cyclin-dependent kinase inhibitor 1B (CDKN1B or P27KIP1) 1 has been reported as a non-canonical inhibitor to mTOR signaling in mouse embryo fibroblasts (MEFs). However, the mechanisms underlying P27KIP1-mTOR axis are yet-to-be uncovered. Here, we find that micropeptide human small regulatory polypeptide of amino acid response (hSPAR）, through its C-terminus (hSPAR-C), inhibits E3 ligase tripartite motif containing 21 (TRIM21)-mediated P27KIP1 degradation and causes P27KIP1’s cytoplasmic accumulation in breast cancer cells. Interestingly, hSPAR/hSPAR-C also serves as an inhibitor to glutamine transporter SLC38A2 and remarkably decreases the cellular glutamine level specifically in cancer cells. The resulted glutamine deprivation sequentially triggers translocation of cytoplasmic P27KIP1 to lysosomes, where P27KIP1 disrupts Ragulator complex and suppresses mTOR complex 1 (mTORC1) assembly. Administration of hSPAR or hSPAR-C dramatically impedes breast cancer cell proliferation and xenografic tumor growth. Collectively, we define hSPAR as an intrinsic molecule to control cellular glutamine level and a previously-unidentified tumor suppressor by promoting accumulation and lysosomal-localization of P27KIP1 to inhibit mTORC1 assembly. |
| Institute: | University of Science and Technology of China |
| Last Name: | Wang |
| First Name: | Wei |
| Address: | Division of Life Sciences and Medicine, 443 Huangshan Road, Hefei city, Anhui Province, 230022, China |
| Email: | WW571@mail.ustc.edu.cn |
| Phone: | 18604523231 |
Summary of all studies in project PR002173
| Study ID | Study Title | Species | Institute | Analysis (* : Contains Untargted data) |
Release Date | Version | Samples | Download (* : Contains raw data) |
|---|---|---|---|---|---|---|---|---|
| ST003531 | Micropeptide hSPAR, a glutamine regulator, suppresses tumor growth via TRIM21-P27KIP1-mTOR pathway - human MDA-MB-231 breast cancer cell | Homo sapiens | University of Science and Technology of China | MS | 2025-01-06 | 1 | 12 | Uploaded data (3.3M)* |
| ST003532 | Micropeptide hSPAR, a glutamine regulator, suppresses tumor growth via TRIM21-P27KIP1-mTOR pathway - HEK293T human embryonic kidney cells | Homo sapiens | University Of Science And Technology of China | MS | 2025-01-06 | 1 | 9 | Uploaded data (2.6M)* |
