Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0155339 (Brown)
 12,436 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The crystal structure of human cyclin H has been solved at 2.6 A resolution by the MIR method and refined to an R-factor of 23.1%. The core of the molecule consists of two helical repeats adopting the canonical cyclin fold already observed in the structures of cyclin A [Brown et al. (1995) Structure 3, 1235-1247; Jeffrey et al. (1995) Nature 376, 313-320; Russo et al. (1996) Nature 382, 325-331] and TFIIB [Nikoilov et al. (1995) Nature 377, 119-128]. The N-terminal and C-terminal residues form a new domain built on two long helices interacting essentially with the first repeat of the molecule.
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PMID:The crystal structure of human cyclin H. 894 15

Neuronal Cdk5 activator (Nck5a) differs from other cyclin-dependent kinase (Cdk) activators in that its amino acid sequence is only marginally similar to the cyclin consensus sequence. Nevertheless, computer modeling has suggested that Nck5a contains the cyclin-fold motif recently identified in the crystal structure of cyclin A. In the present study, a number of truncation mutants and substitution mutants of the Nck5a were produced and tested for the Cdk5 activation and Cdk5 binding activity. The active domain of Nck5a determined by using the truncation mutants consists of the region spanning residues 150 to 291. The size of Nck5a active domain is essentially the same as that of cyclin A required for Cdk2 activation (Lees, E. M., and Harlow, E. (1993) Mol. Cell. Biol. 13, 1194-1201). The change, or the lack of change, in Cdk5 activation activity observed with a number of substitution mutants may be understood on the basis of structure and function relationship of cyclin A. These results provide support to the previous suggestion (Brown, N. R., Noble, M. E. M., Endicott, J. A., Garman, E. F., Wakatsuki, S., Mitchell, E., Rasmussen, B., Hunt, T., and Johnson, L. N. (1995) Structure 3, 1235-1247) that the activation domain of Nck5a adopts a conformation similar to that of cyclin A. They also provide a partial answer to the question of how Nck5a, a non-cyclin, activates a cyclin-dependent kinase.
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PMID:Cyclin-dependent kinase 5 (Cdk5) activation domain of neuronal Cdk5 activator. Evidence of the existence of cyclin fold in neuronal Cdk5a activator. 913 76

One of the pathologic complications of exudative (i.e. wet-type) age-related macular degeneration (AMD) is choroidal neovascularization (CNV). The aim of this study was to investigate whether chronic and heavy alcohol consumption influenced the development of CNV in a rat model. The oxidative metabolism of alcohol is minimal or absent in the eye, so that ethanol is metabolized via a nonoxidative pathway to form fatty acid ethyl esters (FAEE). Fatty acid ethyl ester synthase (FAEES) was purified from the choroid of Brown Norway (BN) rats. The purified protein was 60 kDa in size and the antibody raised against this protein showed a single band on western blot. BN rats on a regular diet were fed alcohol for 10 weeks. Control rats were fed water with a regular diet and pair-fed control rats were fed regular diet, water and glucose. We found that FAEES activity was increased 4.0-fold in the choroid of alcohol-treated rats compared with controls. The amount of ethyl esters produced in the choroid of 10 week alcohol-fed rats was 7.4-fold more than rats fed alcohol for 1 week. The increased accumulation of ethyl esters was associated with a 3.0-fold increased expression of cyclin E and cyclin E/CDK2; however, the level of the cyclin kinase inhibitor, p27Kip, did not change. The increased accumulation of ethyl esters was also associated with 3.0-fold decreased expression of APN in the choroid. We also found that the size of CNV increased by 28% in alcohol-fed rats. Thus, our study showed that chronic, heavy alcohol intake was associated with both an increased accumulation of ethyl esters in the choroid and an exacerbation of the CNV induced by laser treatment. These results may provide insight into the link between heavy alcohol consumption and exudative AMD.
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PMID:Alcohol linked to enhanced angiogenesis in rat model of choroidal neovascularization. 1668 28

Age-dependent epithelial cell hyperplasia in the dorsal and lateral lobes of Brown Norway rats is analogous to benign prostatic hyperplasia in aging men. A major question is whether differential lobe-specific and age-dependent proliferation of cells, rather than cell survival, contributes to the hyperplasia. Although serum testosterone (T) levels decline in aged rats, active cell proliferation was detected as Ki67-positive cells in the dorsal and lateral lobes. We determined whether androgens differentially affect cell proliferation and cell-cycle regulatory proteins in the prostate lobes of young and aged rats. Castrated rats were treated with different doses of T to restore serum levels to those of intact young or aged rats. Rates of cell proliferation, measured by 5-bromodeoxyuridine labeling, peaked after 3-d T treatment in all lobes. 5-bromodeoxyuridine-labeling indices were higher in the dorsal and lateral lobes of aged than of young rats with equivalent serum T levels. No age-dependent difference was seen in the ventral lobe. Cell proliferation was marked by increased levels of cyclins D1 and E and cyclin-dependent kinases 4 and 6, decreased p27 and increased phosphorylation of Rb. Levels of cyclins D1 and E were higher in the dorsal and lateral lobes of intact and T-treated aged than young rats. Confocal immunofluorescent microscopy documented changes in cyclin-dependent kinase 4 and cyclin D1 subcellular localization. Cyclin D1 nuclear localization correlated with the time frame for cell proliferation. In conclusion, rates of cell proliferation and levels of cell-cycle regulatory proteins that control the G1/S transition exhibit lobe-specific and age-dependent differences in response to androgens.
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PMID:Cell proliferation and expression of cell cycle regulatory proteins that control the G1/S transition are age dependent and lobe specific in the Brown Norway rat model of prostatic hyperplasia. 1796 42