Muscle cell survival mediated by the transcriptional coactivators p300 and PCAF displays different requirements for acetyltransferase activity

Kuninger, David; Wright, A. Stuart; Rotwein, Peter

doi:10.1152/ajpcell.00056.2006

Cited by 11 publications

(9 citation statements)

References 61 publications

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“…In the activation of the osteocalcin promoter by vitamin D 3 in osteoblastic cells, Sierra et al (18) demonstrated that although p300 and PCAF have additive effects on the osteocalcin promoter, the intrinsic HAT activity of p300 is dispensable. Similarly, for muscle cell differentiation and survival, the HAT activity of PCAF was required, but not that of p300 (28,43). In contrast, the HAT activity of p300 was essential for COX-2 gene transcription (36) and Notch intracellular domain signaling (37).…”

Section: Discussionmentioning

confidence: 99%

Parathyroid Hormone Activation of Matrix Metalloproteinase-13 Transcription Requires the Histone Acetyltransferase Activity of p300 and PCAF and p300-dependent Acetylation of PCAF

Lee

Partridge

2010

Journal of Biological Chemistry

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Parathyroid hormone (PTH) regulates the transcription of many genes involved in bone remodeling in osteoblasts. One of these genes is matrix metalloproteinase-13 (MMP-13), which is involved in bone remodeling and early stages of endochondral bone formation. We have previously shown that Mmp-13 gene expression is highly induced by PTH treatment in osteoblastic UMR 106-01 cells, as well as primary osteoblasts. Here, we show that p300/CBP-associated factor (PCAF), in addition to p300 and Runx2, is required for PTH activation of Mmp-13 transcription. PCAF was increasingly recruited to the MMP-13 proximal promoter region after PTH treatment, and this was associated with an increase in RNA polymerase II recruitment and histone acetylation. In addition, PTH treatment increased the acetylation of PCAF, a process that required p300. Knockdown of PCAF, p300, or Runx2 by siRNA decreased Mmp-13 mRNA expression after PTH treatment in both UMR 106-01 cells and primary osteoblasts. We found that there is a mutual dependence between p300 and PCAF to be recruited to the Mmp-13 promoter after PTH treatment. In promoter-reporter assays, p300 and PCAF had an additive effect on PTH stimulation of MMP-13 promoter activity, and this required their histone acetyltransferase activity. Our findings demonstrate that PCAF acts downstream of PTH signaling as a transcriptional coactivator that is required for PTH stimulation of MMP-13 transcription. PCAF cooperates with p300 and Runx2 to mediate PTH activation of MMP-13 transcription. PTH2 is a peptide hormone that plays a central role in regulating serum ion concentrations. Secreted from the parathyroid glands in response to low serum calcium levels, PTH has two primary sites of action, bone and kidney. In bone, PTH stimulates the release of calcium and phosphate ions from the bone mineral matrix, leading to bone degradation such that PTH is classically known as a catabolic agent in bone remodeling.However, when administered intermittently, PTH has an anabolic effect that leads to increased bone mass. Binding of PTH to its receptor, PTH1R, on the surface of osteoblasts leads to the activation of many different signaling pathways, including protein kinase A (PKA)-and protein kinase C (PKC)-dependent pathways, as well as calcium ion channels (reviewed in Ref. 1). This eventually leads to a significant change in gene expression in osteoblasts (2). Microarray analyses from our laboratory demonstrated that the catabolic effect of PTH on bone predominantly occurs through PKA-dependent signaling (3).MMP-13 is a collagenase that is expressed in chondrocytes, osteoblasts, and osteocytes. It plays an essential role in early stages of endochondral bone formation, and its expression is increased in pathological conditions such as osteoarthritis, rheumatoid arthritis, and tumor metastasis (4 -6). Mmp-13 gene expression is highly stimulated by PTH in osteoblastic UMR 106-01 cells (7), as well as in vivo (8). The relevance of MMP-13 and PTH has been demonstrated in vivo by the decreased expression of MMP-...

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Section: Discussionmentioning

confidence: 99%

Parathyroid Hormone Activation of Matrix Metalloproteinase-13 Transcription Requires the Histone Acetyltransferase Activity of p300 and PCAF and p300-dependent Acetylation of PCAF

Lee

Partridge

2010

Journal of Biological Chemistry

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“…Regarding neuronal systems in general, the FGF-system is known to play important roles in neuronal survival, axonal guidance, target recognition and maturation of neuromuscular junctions (for review see [41]); processes which are affected by SMN. In muscle, FGFs carry out muscle intrinsic functions such as muscle cell survival as well as muscle derived support of motoneuron survival [42], [43], [44].…”

Section: Discussionmentioning

confidence: 99%

Analysis of the Fibroblast Growth Factor System Reveals Alterations in a Mouse Model of Spinal Muscular Atrophy

et al. 2012

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The monogenetic disease Spinal Muscular Atrophy (SMA) is characterized by a progressive loss of motoneurons leading to muscle weakness and atrophy due to severe reduction of the Survival of Motoneuron (SMN) protein. Several models of SMA show deficits in neurite outgrowth and maintenance of neuromuscular junction (NMJ) structure. Survival of motoneurons, axonal outgrowth and formation of NMJ is controlled by neurotrophic factors such as the Fibroblast Growth Factor (FGF) system. Besides their classical role as extracellular ligands, some FGFs exert also intracellular functions controlling neuronal differentiation. We have previously shown that intracellular FGF-2 binds to SMN and regulates the number of a subtype of nuclear bodies which are reduced in SMA patients. In the light of these findings, we systematically analyzed the FGF-system comprising five canonical receptors and 22 ligands in a severe mouse model of SMA. In this study, we demonstrate widespread alterations of the FGF-system in both muscle and spinal cord. Importantly, FGF-receptor 1 is upregulated in spinal cord at a pre-symptomatic stage as well as in a mouse motoneuron-like cell-line NSC34 based model of SMA. Consistent with that, phosphorylations of FGFR-downstream targets Akt and ERK are increased. Moreover, ERK hyper-phosphorylation is functionally linked to FGFR-1 as revealed by receptor inhibition experiments. Our study shows that the FGF system is dysregulated at an early stage in SMA and may contribute to the SMA pathogenesis.

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“…In addition, spermatocytes, interstitial cells of adult testis and granulosa cells of the cumulus oophorus (cumulus cells) as well as mural granulosa cells in adult ovary exhibit EFhd1 expression [16,88]. EFhd1 is also expressed in IGF-II-deficient murine C2 myoblasts [89]. There, efhd1 mRNA ceases in the absence of the transcriptional co-activator p300 [89].…”

Section: Efhd1mentioning

confidence: 99%

“…EFhd1 is also expressed in IGF-II-deficient murine C2 myoblasts [89]. There, efhd1 mRNA ceases in the absence of the transcriptional co-activator p300 [89]. Healthy human renal tissue expresses efhd1 mRNA [90] and in murine kidney the collecting ducts, but not the glomeruli, reveal EFhd1 [16,88].…”

Section: Efhd1mentioning

confidence: 99%

“…Gene expression profiling of IGF-II-deficient myoblasts that undergo apoptosis when incubated in differentiation-promoting medium revealed new mediators of CBP/p300 promoted survival. Myoblasts expressing CBP/p300 showed a 17-fold up-regulation of EFhd1 [89]. This indicates that EFhd1 might be a factor causing CBP/p300 mediated survival in muscle cells.…”

Section: Efhd1mentioning

confidence: 99%

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Fraternal twins: Swiprosin-1/EFhd2 and Swiprosin-2/EFhd1, two homologous EF-hand containing calcium binding adaptor proteins with distinct functions

2011

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Changes in the intracellular calcium concentration govern cytoskeletal rearrangement, mitosis, apoptosis, transcriptional regulation or synaptic transmission, thereby, regulating cellular effector and organ functions. Calcium binding proteins respond to changes in the intracellular calcium concentration with structural changes, triggering enzymatic activation and association with downstream proteins. One type of calcium binding proteins are EF-hand super family proteins. Here, we describe two recently discovered homologous EF-hand containing adaptor proteins, Swiprosin-1/EF-hand domain containing 2 (EFhd2) and Swiprosin-2/EF-hand domain containing 1 (EFhd1), which are related to allograft inflammatory factor-1 (AIF-1). For reasons of simplicity and concision we propose to name Swiprosin-1/EFhd2 and Swiprosin-2/EFhd1 from now on EFhd2 and EFhd1, according to their respective gene symbols. AIF-1 and Swiprosin-1/EFhd2 are already present in Bilateria, for instance in Drosophila melanogaster and Caenhorhabditis elegans. Swiprosin-2/EFhd1 arose later from gene duplication in the tetrapodal lineage. Secondary structure prediction of AIF-1 reveals disordered regions and one functional EF-hand. Swiprosin-1/EFhd2 and Swiprosin-2/EFhd1 exhibit a disordered region at the N-terminus, followed by two EF-hands and a coiled-coil domain. Whereas both proteins are similar in their predicted overall structure they differ in a non-homologous stretch of 60 amino acids just in front of the EF-hands. AIF-1 controls calcium-dependent cytoskeletal rearrangement in innate immune cells by means of its functional EF-hand. We propose that Swiprosin-1/EFhd2 as well is a cytoskeleton associated adaptor protein involved in immune and brain cell function. Pro-inflammatory conditions are likely to modulate expression and function of Swiprosin-1/EFhd2. Swiprosin-2/EFhd1, on the other hand, modulates apoptosis and differentiation of neuronal and muscle precursor cells, probably through an association with mitochondria. We suggest furthermore that Swiprosin-2/EFhd1 is part of a cellular response to oxidative stress, which could explain its pro-survival activity in neuronal, muscle and perhaps some malignant tissues.

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Muscle cell survival mediated by the transcriptional coactivators p300 and PCAF displays different requirements for acetyltransferase activity

Abstract: . Muscle cell survival mediated by the transcriptional coactivators p300 and PCAF displays different requirements for acetyltransferase activity.

Cited by 11 publications

References 61 publications

Parathyroid Hormone Activation of Matrix Metalloproteinase-13 Transcription Requires the Histone Acetyltransferase Activity of p300 and PCAF and p300-dependent Acetylation of PCAF

Parathyroid Hormone Activation of Matrix Metalloproteinase-13 Transcription Requires the Histone Acetyltransferase Activity of p300 and PCAF and p300-dependent Acetylation of PCAF

Analysis of the Fibroblast Growth Factor System Reveals Alterations in a Mouse Model of Spinal Muscular Atrophy

Fraternal twins: Swiprosin-1/EFhd2 and Swiprosin-2/EFhd1, two homologous EF-hand containing calcium binding adaptor proteins with distinct functions

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