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S Muralidhar

Publications and source records attributed to S Muralidhar.

23 records · Page 2Linked to original sources
PubMed1996

Human cytomegalovirus mtrII oncoprotein binds to p53 and down-regulates p53-activated transcription.

The 79-amino-acid (79-aa) open reading frame (UL111a) gene within morphological transforming region II (mtrII) of human cytomegalovirus strain Towne has been shown to transform rodent cells in vitro (J. Thompson, J. Doniger, and L. J. Rosenthal, Arch. Virol. 136:161-172, 1994). Moreover, a translation termination linker (TTL) mutant of mtrII that coded for the first 49 aa of mtrII oncoprotein (designated TTL49) was sufficient for malignant transformation, whereas a TTL mutant that coded for the first 24 aa (designated TTL24) was not. The current study demonstrates the binding of mtrII oncoprotein to the tumor suppressor protein p53 both in vivo using transiently transfected cells and in vitro using labeled proteins. Furthermore, the C-terminally truncated mtrII protein TTL49, but not truncated protein TTL24, bound to p53. The mtrII binding domain mapped to the N-terminal region of p53, residues 1 to 106, with a critical region from aa 27 to 44, whereas the p53 binding domain of mtrII protein was the first 49 aa. Furthermore, mtrII inhibited p53-activated transcription, indicating its ability to alter p53-directed cellular regulatory mechanisms. mtrII oncoprotein was detected both in stably transfected NIH 3T3 cell lines and human cytomegalovirus-infected HEL 299 cells (as early as 12 h after infection) in the perinuclear region and in the nucleus. mtrII-transformed cell lines, at both early and late passage, exhibited high levels of p53 with a 15-fold-extended half-life. However, p53-activated transcription was suppressed in these cells in spite of the increased p53 levels. Finally, the results with wild-type mtrII and its TTL mutants with respect to p53 binding, p53-activated transcription, and transforming ability suggest that the mechanism of mtrII transformation is linked to both p53 binding and disruption of p53 cell regulation.

3T3 Cells↗
PubMed1994

Site-directed mutagenesis of adeno-associated virus type 2 structural protein initiation codons: effects on regulation of synthesis and biological activity.

It has been shown that two of the three adeno-associated virus type 2 capsid proteins, B and C, are synthesized from a single spliced transcript. Protein C arises from an AUG codon at nucleotide 2810, whereas protein B is initiated by a unique eucaryotic initiation codon (ACG) that lies 65 triplets upstream from the C origin. The third capsid component, protein A, is synthesized from a second spliced transcript which uses an alternative 3' acceptor site. In this study we used oligonucleotide-directed mutagenesis to confirm the positions of the B initiation codon and the 3' acceptor sites for the alternatively spliced B/C and A protein messages. We also located definitively the protein A initiation codon, an AUG triplet mapping to nucleotide 2203. Mutagenesis of the B initiator permitted a direct test of the effect of increased B initiator strength on the translational efficiencies of the B and C proteins. It was found that conversion of the relatively inefficient protein B initiator (ACG) to an AUG enhanced the level of B synthesis while abolishing the synthesis of C from its downstream AUG initiator. Protein C synthesis thus depends on the strength of the B initiator, i.e., the relatively higher levels of C (approximately 20-fold greater than B) must result from frequent readthrough of the weak B initiator. Finally, we examined the abilities of mutants deficient in the synthesis of A, B, or C to produce infectious virions. We found that at least two of the structural proteins, B and C, are required for the production of infectious virions and that sequestration of single-stranded adeno-associated virus genomes from the pool of replicating DNA molecules does not occur in the absence of either of these proteins.

Blotting, Northern↗
PubMedDate not supplied

Treatment of widespread alopecia areata in young patients with monthly oral corticosteroid pulse.

Sixteen patients up to 18 years of age with widespread alopecia areata (AA) were recruited for the study. They included 10 patients with extensive AA (> or = 40% loss of scalp hair and or more than 10 patches scattered over the scalp and body) and 3 each with alopecia totalis and circumscribed alopecia areata. Patients were divided into two groups. In group A, aged 12 to 18 years, patients received 300 mg of prednisolone in a monthly oral pulse; in group B, aged 3 to 11 years, patients received betamethasone sodium phosphate as soluble tablets or syrup equivalent to prednisolone 5 mg/kg body weight every month. The pulsed doses of corticosteroid were continued for a minimum of three doses or until cosmetically acceptable hair growth was obtained. All patients but one 5-year-old girl received a minimum of three doses. Excellent hair growth was obtained in 9 (60%) of 15 patients evaluated at 6 months. Four patients out of 13 (>12 month follow-up), including two each in group A and B, developed a localized relapse during mean follow-up of 16.4 and 33.7 months in group A and B, respectively. Side effects of pulsed corticosteroid were minimal and were recorded in two patients (transient giddiness and headache, epigastric burning in one each). We recommend pulsed doses of prednisolone as one of the modalities in the treatment of widespread AA in young patients, including children.

Administration, Oral↗