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is the first major gene of litter size identified in sheep. However, the molecular mechanism of the mutation that increases the ovulation rate in sheep is still unclear. In recent years, it has been demonstrated that BMPR1B activity is regulated by the small molecule repressor protein FKBP1A, which acts as a key activity switch of the BMPR1B in the BMP/SMAD pathway. The mutation is located close to the binding site of FKBP1A and BMPR1B. In this review, we summarize the structure of BMPR1B and FKBP1A proteins, and clarify the spatial interactive domains of the two proteins with respect to the location of the mutation. Then the relationship between the mutation and the degree of affinity of the two proteins are predicted. Finally, the hypothesis that mutation causes change of activity in BMP/SMAD pathway by affecting the intensity of the interactions between BMPR1B and FKBP1A is proposed. This hypothesis provides a new clue to investigate the molecular mechanism of mutation affecting ovulation rate and litter size in sheep.
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http://dx.doi.org/10.16288/j.yczz.22-366 | DOI Listing |
Am J Hematol
September 2025
Nephrology Division and Endocrine Unit, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA.
The bone morphogenetic protein (BMP)-SMAD signaling pathway is central to regulating hepcidin, the master regulator of systemic iron homeostasis. We have previously demonstrated that BMP6, BMP2, and, to a lesser extent, BMP5 are the major ligands contributing to hepcidin and iron homeostasis regulation in vivo. Hemojuvelin (HJV) and homeostatic iron regulator (HFE) are hepcidin modulators that are mutated in hereditary hemochromatosis.
View Article and Find Full Text PDFOsteoporos Sarcopenia
June 2025
School of Medicine, Hallym University, Chuncheon, South Korea.
SP7, also known as Osterix, is a zinc finger-containing transcription factor, plays a crucial role in osteoblast differentiation and bone formation. This review examines the molecular mechanisms underlying SP7's regulatory functions, highlighting its interactions with key signaling pathways such as BMP-SMAD, Wnt/β-catenin, and HIF-1α. SP7 acts downstream of RUNX2 to regulate osteogenic gene expression, including collagen Type I Alpha 1 (COL1A1), alkaline phosphatase (ALP) and osteocalcin (OCN).
View Article and Find Full Text PDFFront Cell Dev Biol
July 2025
Xinjiang Key Laboratory of Mental Development and Learning Science, School of Psychology, Xinjiang Normal University, Urumqi, Xinjiang, China.
BMPR1B, a type I receptor in the BMP/Smad signaling pathway, was the first major gene identified in sheep () to regulate key reproductive traits such as ovulation rate (OR) and litter size (LS). Despite its critical role in reproductive performance, the transcriptional regulatory mechanisms governing ovine BMPR1B expression remain poorly understood. This study identified the promoter region of the BMPR1B gene and revealed that transcription factor ELK1 regulates its transcriptional activity.
View Article and Find Full Text PDFBiol Direct
July 2025
Department of Hepatobiliary Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710061, Shaanxi, China.
Adv Exp Med Biol
July 2025
Center for Translational Biomedical Iron Research, Department of Pediatric Hematology, Oncology and Immunology, University of Heidelberg, Heidelberg, Germany.
Disorders of iron metabolism pose a global health challenge. Over the past two decades, novel regulators of systemic iron homeostasis have been identified that can be manipulated for therapeutic purposes. In this context, inbred and genetically modified mice have proven to be valuable tools enabling precise investigation of gene functions and testing of new pharmacological treatments that in some cases have reached the clinical stage.
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