Pin1 regulates parathyroid hormone mRNA stability

Kumar, Rajiv

doi:10.1172/jci40784

Cited by 20 publications

(16 citation statements)

References 48 publications

(51 reference statements)

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“…27,29 Both proteins are regulated by changes in sCa 2+ and phosphate and are altered in CKD. 27,30,130 …”

Section: The Regulation Of Pth Synthesismentioning

confidence: 99%

“…Stabilized mRNA undergoes translation in ribosomes, whereas destabilized mRNA undergoes deadenylation, decapping, and degradation in exosomes or P-bodies. (Adapted from reference 130 with permission from the American Society for Clinical Investigation.) (B) Processing of mRNA-encoding PTH .…”

Section: Figurementioning

confidence: 99%

“…Abbreviation: P, phosphate. (Adapted from reference 130 with permission from the American Society for Clinical Investigation. )…”

Section: Figurementioning

confidence: 99%

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The Regulation of Parathyroid Hormone Secretion and Synthesis

Kumar

Thompson

2011

Journal of the American Society of Nephrology

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176

119

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Secondary hyperparathyroidism classically appears during the course of chronic renal failure and sometimes after renal transplantation. Understanding the mechanisms by which parathyroid hormone (PTH) synthesis and secretion are normally regulated is important in devising methods to regulate overactivity and hyperplasia of the parathyroid gland after the onset of renal insufficiency. Rapid regulation of PTH secretion in response to variations in serum calcium is mediated by G-protein coupled, calcium-sensing receptors on parathyroid cells, whereas alterations in the stability of mRNA-encoding PTH by mRNA-binding proteins occur in response to prolonged changes in serum calcium. Independent of changes in intestinal calcium absorption and serum calcium, 1α,25-dihydroxyvitamin D also represses the transcription of PTH by associating with the vitamin D receptor, which heterodimerizes with retinoic acid X receptors to bind vitamin D-response elements within the PTH gene. 1α,25-Dihydroxyvitamin D additionally regulates the expression of calcium-sensing receptors to indirectly alter PTH secretion. In 2°HPT seen in renal failure, reduced concentrations of calcium-sensing and vitamin D receptors, and altered mRNA-binding protein activities within the parathyroid cell, increase PTH secretion in addition to the more widely recognized changes in serum calcium, phosphorus, and 1α,25-dihydroxyvitamin D. The treatment of secondary hyperparathyroidism by correction of serum calcium and phosphorus concentrations and the administration of vitamin D analogs and calcimimetic agents may be augmented in the future by agents that alter the stability of mRNA-encoding PTH.

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“…27,29 Both proteins are regulated by changes in sCa 2+ and phosphate and are altered in CKD. 27,30,130 …”

Section: The Regulation Of Pth Synthesismentioning

confidence: 99%

Section: Figurementioning

confidence: 99%

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The Regulation of Parathyroid Hormone Secretion and Synthesis

Kumar

Thompson

2011

Journal of the American Society of Nephrology

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176

119

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“…Ess1 functionally interacts with the transcription initiation factor TFIIB, Ssu72 phosphatase, and Pta1 components of the 3=-end processing machinery to influence gene looping (24). Besides its effects on transcription, Pin1 has been implicated in the control of mRNA stability of three AU-rich element (ARE)-containing mRNAs, namely, those for granulocye-macrophage colony-stimulating factor (GM-CSF), parathyroid hormone (Pth), and transforming growth factor ␤ (TGF-␤), in the cytoplasm (10,25). These effects are mediated via direct association of Pin1 with phosphorylated forms of the ARE-binding proteins AUF1 and KSRP.…”

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confidence: 99%

The Prolyl Isomerase Pin1 Targets Stem-Loop Binding Protein (SLBP) To Dissociate the SLBP-Histone mRNA Complex Linking Histone mRNA Decay with SLBP Ubiquitination

Krishnan

Lam

Fritz

et al. 2012

Molecular and Cellular Biology

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f Histone mRNAs are rapidly degraded at the end of S phase, and a 26-nucleotide stem-loop in the 3= untranslated region is a key determinant of histone mRNA stability. This sequence is the binding site for stem-loop binding protein (SLBP), which helps to recruit components of the RNA degradation machinery to the histone mRNA 3= end. SLBP is the only protein whose expression is cell cycle regulated during S phase and whose degradation is temporally correlated with histone mRNA degradation. Here we report that chemical inhibition of the prolyl isomerase Pin1 or downregulation of Pin1 by small interfering RNA (siRNA) increases the mRNA stability of all five core histone mRNAs and the stability of SLBP. Pin1 regulates SLBP polyubiquitination via the Ser20/Ser23 phosphodegron in the N terminus. siRNA knockdown of Pin1 results in accumulation of SLBP in the nucleus. We show that Pin1 can act along with protein phosphatase 2A (PP2A) in vitro to dephosphorylate a phosphothreonine in a conserved TPNK sequence in the SLBP RNA binding domain, thereby dissociating SLBP from the histone mRNA hairpin. Our data suggest that Pin1 and PP2A act to coordinate the degradation of SLBP by the ubiquitin proteasome system and the exosomemediated degradation of the histone mRNA by regulating complex dissociation.

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“…On the other hand, CypA has a role in renal acidosis 111 , diabetic nephropathy 112 and renal cell carcinoma 113 . Furthermore, Pin1 inhibition affects CKD associated with secondary parathyroidism 114 .…”

Section: The Role Of Ppiases In Ckdmentioning

confidence: 99%

The Role of Peptidyl Prolyl Isomerases in Aging and Vascular Diseases

McClements¹,

Annett²,

Yakkundi³

et al. 2015

CMP

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Peptidyl prolyl isomerases (PPIases) are proteins belonging to the immunophilin family and are characterised by their cis-trans isomerization activity at the X-Pro peptide bond, in addition to their tetratricopeptide repeat (TPR) domain, important for interaction with the molecular chaperone, Hsp90. Due to this unique structure these proteins are able to facilitate proteinprotein interactions which can impact significantly on a range of cellular processes such as cell signalling, differentiation, cell cycle progression, metabolic activity and apoptosis.Malfunction and/or dysregulation of most members of this class of proteins promotes cellular damage and tissue/organ failure, predisposing to ageing and age-related diseases. Many individual genes within the PPIase family are associated with several age-related diseases including cardiovascular diseases (CVDs), atherosclerosis, type II diabetes (T2D), chronic kidney disease (CDK), neurodegeneration, cancer and age-related macular degeneration (AMD), in addition to the ageing process itself. This review will focus on the different roles of PPIases, and their therapeutic/biomarker potential in these age-related vascular diseases.

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Pin1 regulates parathyroid hormone mRNA stability

Abstract: Conflict of interest:The author has declared that no conflict of interest exists.

Cited by 20 publications

References 48 publications

The Regulation of Parathyroid Hormone Secretion and Synthesis

The Regulation of Parathyroid Hormone Secretion and Synthesis

The Prolyl Isomerase Pin1 Targets Stem-Loop Binding Protein (SLBP) To Dissociate the SLBP-Histone mRNA Complex Linking Histone mRNA Decay with SLBP Ubiquitination

The Role of Peptidyl Prolyl Isomerases in Aging and Vascular Diseases

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