ArticleProceedings of the National Academy of Sciences of the United States of America2008
Severe growth retardation and early lethality in mice lacking the nuclear localization sequence and C-terminus of PTH-related protein.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 48 papers.
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Who cites it
48 citing papers in PubMed, 130 citations in OpenAlex.
- Article
- Deletion of PTHrP nuclear localization sequence and carboxyl terminus leads to lung dysplasia.Scientific reports · 2025Article
- The Molecular Biology of Placental Transport of Calcium to the Human Foetus.International journal of molecular sciences · 2025Review
- PTHrP intracrine actions divergently influence breast cancer growth through p27 and LIFR.Breast cancer research : BCR · 2024Article
- Chk2 Modulates Bmi1-Deficiency-Induced Renal Aging and Fibrosis via Oxidative Stress, DNA Damage, and p53/TGFβ1-Induced Epithelial-Mesenchymal Transition.International journal of biological sciences · 2024Article
- The nuclear localization sequence and C-terminus of parathyroid hormone-related protein regulate normal pancreatic islet development and function.General and comparative endocrinology · 2023Article
- Review
- 1,25-Dihydroxyvitamin D Deficiency Accelerates Aging-related Osteoarthritis via Downregulation of Sirt1 in Mice.International journal of biological sciences · 2023Article
- Article
- Mechanisms during Osteogenic Differentiation in Human Dental Follicle Cells.International journal of molecular sciences · 2022Review
- PTHrP induces STAT5 activation, secretory differentiation and accelerates mammary tumor development.Breast cancer research : BCR · 2022Article
- Parathyroid hormone signaling in mature osteoblasts/osteocytes protects mice from age-related bone loss.Aging · 2021Article
- Parathyroid Disease in Pregnancy and Lactation: A Narrative Review of the Literature.Biomedicines · 2021Review
- High endogenous expression of parathyroid hormone-related protein (PTHrP) supports osteogenic differentiation in human dental follicle cells.Histochemistry and cell biology · 2020Article
- The role of cellular senescence in ageing and endocrine disease.Nature reviews. Endocrinology · 2020Review
- Article
- 1,25-Dihydroxyvitamin D protects against age-related osteoporosis by a novel VDR-Ezh2-p16 signal axis.Aging cell · 2020Article
- PTHrP, A Biomarker for CNS Metastasis in Triple-Negative Breast Cancer and Selection for Adjuvant Chemotherapy in Node-Negative Disease.JNCI cancer spectrum · 2020Article
- Treatment with soluble bone morphogenetic protein type 1A receptor fusion protein alleviates irradiation-induced bone loss in mice through increased bone formation and reduced bone resorption.American journal of translational research · 2020Article
- 1,25-Dihydroxyvitamin D exerts an antiaging role by activation of Nrf2-antioxidant signaling and inactivation of p16/p53-senescence signaling.Aging cell · 2019Article
Corrections and comments
- Erratum issued
Authors and funding
9 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Parathyroid hormone (PTH) plays a central role in the regulation of serum calcium and phosphorus homeostasis, while parathyroid hormone-related protein (PTHrP) has important developmental roles. Both peptides signal through the same G protein-coupled receptor, the PTH/PTHrP or PTH type 1 receptor (PTH1R). PTHrP, normally a secreted protein, also contains a nuclear localization signal (NLS) that in vitro imparts functionality to the protein at the level of the nucleus. We investigated this functionality in vivo by introducing a premature termination codon in Pthrp in ES cells and generating mice that express PTHrP (1-84), a truncated form of the protein that is missing the NLS and the C-terminal region of the protein but can still signal through its cell surface receptor. Mice homozygous for the knock-in mutation (Pthrp KI) displayed retarded growth, early senescence, and malnutrition leading postnatally to their rapid demise. Decreased cellular proliferative capacity and increased apoptosis in multiple tissues including bone and bone marrow cells were associated with altered expression and subcellular distribution of the senescence-associated tumor suppressor proteins p16(INK4a) and p21 and the oncogenes Cyclin D, pRb, and Bmi-1. These findings provide in vivo experimental proof that substantiates the biologic relevance of the NLS and C-terminal portion of PTHrP, a polypeptide ligand that signals mainly via a cell surface G protein-coupled receptor.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.