PHIP was isolated as an insulin receptor substrate 1 (IRS-1) interacting protein. To date, the physiological roles of PHIP remain unknown. Here we show that mice lacking PHIP1, the full-length isoform of PHIP, are born at normal size but suffer a 40% growth deficit by weaning. PHIP1 mutant mice develop hypoglycemia and have an average lifespan of 4-5 weeks. PHIP1-deficient mouse embryonic fibroblasts (MEFs) grow markedly slower than wild-type MEFs, but exhibit normal AKT phosphorylation and an increased cell proliferation in response to IGF-1 treatment. Together these results suggest that PHIP1 regulates postnatal growth in an IGF-1/AKT pathway-independent manner.
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http://dx.doi.org/10.1016/j.febslet.2010.08.042 | DOI Listing |
Plant Cell Physiol
January 2025
University of Münster, Department of Biology, Institute of Plant Biology and Biotechnology, Molecular Physiology of Plants, Schlossplatz 7, 48149 Münster, Germany.
The oxidative pentose phosphate pathway (OPPP) plays an important role for the generation of reducing power in all eukaryotes. In plant cells the OPPP operates in several cellular compartments, but as full cycle only in the plastid stroma where it is essential. As suggested by our recent results, OPPP reactions are also mandatory inside peroxisomes, at least during fertilisation.
View Article and Find Full Text PDFCell Death Dis
January 2025
Center for Precision Medicine Research, Marshfield Clinic Research Institute, Marshfield Clinic Health System, Marshfield, WI, USA.
The orphan nuclear receptor NR2E3 has emerged as a potential tumor suppressor, yet its precise mechanisms in tumorigenesis require further investigation. Here, we demonstrate that the full-length protein isoform of NR2E3 instead of its short isoform activates wild-type p53 and is capable of rescuing certain p53 mutations in various cancer cell lines. Importantly, we observe a higher frequency of NR2E3 mutations in three solid tumors compared to the reference population, highlighting its potential significance in tumorigenesis.
View Article and Find Full Text PDFbioRxiv
January 2025
Department of Computer Science, School of Computing and Data Science, University of Hong Kong, Hong Kong, China.
Variant calling using long-read RNA sequencing (lrRNA-seq) can be applied to diverse tasks, such as capturing full-length isoforms and gene expression profiling. It poses challenges, however, due to higher error rates than DNA data, the complexities of transcript diversity, RNA editing events, etc. In this paper, we propose Clair3-RNA, the first deep learning-based variant caller tailored for lrRNA-seq data.
View Article and Find Full Text PDFmedRxiv
February 2024
Center for Alzheimer's and Related Dementias, National Institute on Aging and National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA.
Recently, a novel African ancestry specific Parkinson's disease (PD) risk signal was identified at the gene encoding glucocerebrosidase (). This variant (rs3115534-G) is carried by ~50% of West African PD cases and imparts a dose-dependent increase in risk for disease. The risk variant has varied frequencies across African ancestry groups, but is almost absent in European and Asian ancestry populations.
View Article and Find Full Text PDFmedRxiv
November 2024
Laboratory of Translational Genomics, DCEG, National Cancer Institute, Rockville, MD, USA.
The chromosome 5p15.33 region, which encodes telomerase reverse transcriptase (TERT), harbors multiple germline variants identified by genome-wide association studies (GWAS) as risk for some cancers but protective for others. We characterized a variable number tandem repeat within intron 6 (VNTR6-1, 38-bp repeat unit) and observed a strong association between VNTR6-1 alleles (Short: 24-27 repeats, Long: 40.
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