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Ribonucleotide reductase small subunit p53R2 suppresses MEK–ERK activity by binding to ERK kinase 2
Piao, C,Jin, M,Kim, H B,Lee, S M,Amatya, P N,Hyun, J -W,Chang, I -Y,You, H J Macmillan Publishers Limited 2009 Oncogene Vol.28 No.21
The p53-dependent RR small subunit (p53R2) protein, a newly identified member of the ribonucleotide reductase family, plays a key role in the p53-dependent cellular response to DNA. Several recent studies have suggested that p53R2 also plays an important role in suppressing the invasive potential of human cancer cells. However, the cellular mechanism that regulates invasiveness remains largely unknown. In this study, we show that p53R2 interacts with MEK2 (extracellular signal-regulated kinase (ERK) kinase 2–mitogen-activated protein kinase (MAPK) kinase 2), the molecule immediately upstream of ERK in the Ras–Raf–MAPK signaling cascade. In co-immunoprecipitation and immunofluorescence analyses, we found that p53R2 and MEK2 interact physically in cultured mammalian cells, and that the p53R2 segment comprising amino acids 161–206 is critical for this interaction. Moreover, serum-induced phosphorylation of MEK1/2 and ERK1/2 was greatly augmented in human cancer cells expressing small-interfering RNA against p53R2. On the other hand, phosphorylation of MEK1/2 and ERK1/2 in human cancer cells was markedly attenuated by overexpression of p53R2. Furthermore, MEK2 was required for p53R2 knockdown-induced enhancement of the invasive ability and anchorage-independent growth of human lung cancer H1299 cells. Taken together, these findings show that p53R2 negatively modulates serum-induced MEK–ERK activity and inhibits the MEK–ERK-mediated malignancy potential of human cancer cells.Oncogene (2009) 28, 2173–2184; doi:10.1038/onc.2009.84; published online 27 April 2009
Alteration by p11 of mGluR5 localization regulates depression-like behaviors
Lee, K-W,Westin, L,Kim, J,Chang, J C,Oh, Y-S,Amreen, B,Gresack, J,Flajolet, M,Kim, D,Aperia, A,Kim, Y,Greengard, P Macmillan Publishers Limited 2015 Molecular psychiatry Vol.20 No.12
Mood disorders and antidepressant therapy involve alterations of monoaminergic and glutamatergic transmission. The protein S100A10 (p11) was identified as a regulator of serotonin receptors, and it has been implicated in the etiology of depression and in mediating the antidepressant actions of selective serotonin reuptake inhibitors. Here we report that p11 can also regulate depression-like behaviors via regulation of a glutamatergic receptor in mice. p11 directly binds to the cytoplasmic tail of metabotropic glutamate receptor 5 (mGluR5). p11 and mGluR5 mutually facilitate their accumulation at the plasma membrane, and p11 increases cell surface availability of the receptor. Whereas p11 overexpression potentiates mGluR5 agonist-induced calcium responses, overexpression of mGluR5 mutant, which does not interact with p11, diminishes the calcium responses in cultured cells. Knockout of mGluR5 or p11 specifically in glutamatergic neurons in mice causes depression-like behaviors. Conversely, knockout of mGluR5 or p11 in GABAergic neurons causes antidepressant-like behaviors. Inhibition of mGluR5 with an antagonist, 2-methyl-6-(phenylethynyl)pyridine (MPEP), induces antidepressant-like behaviors in a p11-dependent manner. Notably, the antidepressant-like action of MPEP is mediated by parvalbumin-positive GABAergic interneurons, resulting in a decrease of inhibitory neuronal firing with a resultant increase of excitatory neuronal firing. These results identify a molecular and cellular basis by which mGluR5 antagonism achieves its antidepressant-like activity.
Chang, I.Y.,Ohn, T.,Ko, G.S.,Yoon, Y.,Kim, J.W.,Yoon, S.P. Wiley Sons ; Elsevier Science Ltd ; Elsevier Scien 2012 Journal of chemical neuroanatomy Vol.43 No.1
Cholesterol transport proteins are a prerequisite for neurosteroidogenesis. Steroidogenic acute regulatory protein (StAR)-related lipid transfer (START) domain-containing proteins, such as StAR and START domain-containing 6 (StarD6), are known to be distributed in the brain. Since perinatal hypothyroidism affects cerebellar development, we examined postnatal changes in StAR and StarD6 immunolocalization in the developing cerebellum of control and hypothyroid rats. Pregnant Sprague-Dawley rats were given 0.05% 6-propyl-2-thiouracil (PTU) or water from gestation day 11 until postnatal day (P) 28, and were then killed together with age-matched control rats. As shown by calbindin D-28k immunostaining, the developing cerebellar cytoarchitecture and Purkinje cells were affected by PTU-induced hypothyroidism as compared to control rats. The immunolocalization of StAR and StarD6 generally followed the maturation pattern of Purkinje cells from the vermis to the cerebellar hemisphere. StAR immunostaining first appeared in the Purkinje cells of the vermis at P7 in both control and hypothyroid rats. In control rats, a few StarD6 immunoreactive cells were seen at birth and a nuclear localization of StarD6 in Purkinje cells was obvious at P14. PTU-induced hypothyroidism delayed the appearance of StarD6 immunopositive cells until P7. Moreover, the nuclear localization of StarD6 in PTU-treated rats was not obvious at P14. An adult-like distribution of StAR and StarD6 was achieved by P21 in control and hypothyroid rats. These results suggest that StarD6 may affect the development of Purkinje cells during the first and second postnatal weeks, a known period of thyroid hormone action.
Quan, Z.-X.,Xiao, Y.-P.,Roh, S. W.,Nam, Y.-D.,Chang, H.-W.,Shin, K.-S.,Rhee, S.-K.,Park, Y.-H.,Bae, J.-W. Microbiology Society 2008 International journal of systematic and evolutiona Vol.58 No.6
<P>A Gram-negative, non-spore-forming, non-motile, yellow-pigmented, strictly aerobic bacterial strain, designated En5(T), was isolated from the East Sea of Korea and was subjected to a polyphasic taxonomy study. Strain En5(T) grew optimally at 30 degrees C, in the presence of 1-3 % (w/v) NaCl and at pH 5.3-7.6. The major respiratory lipoquinone was MK-6 and the major fatty acids were iso-C(15 : 0), iso-C(17 : 0) 3-OH and iso-C(17 : 1)omega9c. The DNA G+C content of strain En5(T) was 30.1 mol%. Phylogenetic analyses based on 16S rRNA gene sequences showed that strain En5(T) formed a distinct evolutionary lineage within the family Flavobacteriaceae and shared 93 % sequence similarity with the type strains of both Galbibacter mesophilus and Zhouia amylolytica. On the basis of its phenotypic and phylogenetic properties, strain En5(T) is suggested to represent a novel species of a new genus in the family Flavobacteriaceae, for which the name Joostella marina gen. nov., sp. nov. is proposed. The type strain is En5(T) (=KCTC 12518(T)=DSM 19592(T)=CGMCC 1.6973(T)).</P>
Safety assessment of trans-tympanic photobiomodulation
Moon, T. H.,Lee, M. Y.,Jung, J. Y.,Ahn, J. C.,Chang, S. Y.,Chung, P. S.,Rhee, C. K.,Kim, Y. H.,Suh, M. W. Springer Science + Business Media 2016 Lasers in medical science Vol.31 No.2
<P>We evaluated functional and morphological changes after trans-tympanic laser application using several different powers of photobiomodulation (PBM). The left (L) ears of 17 rats were irradiated for 30 min daily over 14 days using a power density of 909.1 (group A, 5040 J), 1136.4 (group B, 6300 J), and 1363.6 (group C, 7560 J) mW/cm(2). The right (N) ears served as controls. The safety of PBM was determined by endoscopic findings, auditory brainstem response (ABR) thresholds, and histological images of hair cells using confocal microscopy, and light microscopic images of the external auditory canal (EAC) and tympanic membrane (TM). Endoscopic findings revealed severe inflammation in the TM of C group; no other group showed damage in the TM. No significant difference in ABR threshold was found in the PBM-treated groups (excluding the group with TM damage). Confocal microscopy showed no histological difference between the AL and AN, or BL and BN groups. However, light microscopy showed more prominent edema, inflammation, and vascular congestion in the TM of BL ears. This study found a dose-response relationship between laser power parameters and TM changes. These results will be useful for defining future allowance criteria for trans-tympanic laser therapies.</P>