Pathogenesis of Noonan Syndrome is Modulated by NOC2L, a Novel Interactor of LZTR1 Leading to Impaired P53 Signalling
NOC2L and p53 form a complex which dictates p53 activation. We demonstrate a previously unknown interaction between NOC2L and LZTR1 and hypothesise that LZTR1 acts as a binding factor modulating activity of this complex. Since NOC2L negatively regulates p53, its upregulation leads to p53-mediated transcription inhibition. LZTR1 attenuation due to genetic mutations associated with NS, potentiate NOC2L activity leading to reduced apoptosis and a compensatory increase in autophagy.
Authors
- Carles Gaston‐Massuet (ORCID: https://orcid.org/0000-0002-6793-3118)
- Miho Ishida (ORCID: https://orcid.org/0000-0002-4769-2273)
- Helen L. Storr (ORCID: https://orcid.org/0000-0002-9963-1931)
- Avinaash Maharaj (ORCID: https://orcid.org/0000-0001-8051-3866)
- Débora Romeo Bertola (ORCID: https://orcid.org/0000-0002-4701-6777)
- Liam James McGuffin (ORCID: https://orcid.org/0000-0003-4501-4767)
- Juliana Chizo Agwu (ORCID: https://orcid.org/0000-0002-8593-187X)
- Sumana Chatterjee (ORCID: https://orcid.org/0000-0001-5273-0046)
Institutions
- Universidade de São Paulo (BR)
- Birmingham Dental Hospital (GB)
- Hospital Universitário da Universidade de São Paulo (BR)
- William Harvey Research Institute (GB)
- University of Reading (GB)
- University of Birmingham (GB)
Publication Details
- Journal
- The Journal of Clinical Endocrinology & Metabolism
- Published
- 2025-10-31
- DOI
- https://doi.org/10.1210/clinem/dgaf602
- Primary Topic
- Protein Tyrosine Phosphatases
- Type
- article
- Field-Weighted Citation Impact
- 0.00