Mice lacking p27(Kip1) have been created by gene targeting in embryonic stem cells. These mice are larger than the control animals, with thymus, pituitary, and adrenal glands and gonadal organs exhibiting striking enlargement. CDK2 activity is elevated about 10-fold in p27(-/-) thymocytes. Development of ovarian follicles seems to be impaired, resulting in female sterility. Similar to mice with the Rb mutation, the p27(-/-) mice often develop pituitary tumors spontaneously. The retinas of the mutant mice show a disturbed organization of the normal cellular layer pattern. These findings indicate that p27(Kip1) acts to regulate the growth of a variety of cells. Unexpectedly, the cell cycle arrest mediated by TGFbeta, rapamycin, or contact inhibition remained intact in p27(-/-) cells, suggesting that p27(Kip1) is not required in these pathways.
We found an autoimmune serum, K199, that strongly suppresses nuclear membrane assembly in a cell-free system involving a Xenopus egg extract. Four different antibodies that suppress nuclear assembly were affinity-purified from the serum using Xenopus egg cytosol proteins. Three proteins recognized by these antibodies were identified by partial amino acid sequencing to be glyceraldehyde-3-phosphate dehydrogenase (GAPDH), fructose-1,6-bisphosphate aldolase, and the regulator of chromatin condensation 1. GAPDH is known to be a fusogenic protein. To verify the participation of GAPDH in nuclear membrane fusion, authentic antibodies against human and rat GAPDH were applied, and strong suppression of nuclear assembly at the nuclear membrane fusion step was observed. The nuclear assembly activity suppressed by antibodies was recovered on the addition of purified chicken GAPDH. A peptide with the sequence of amino acid residues 70 -94 of GAPDH, which inhibits GAPDH-induced phospholipid vesicle fusion, inhibited nuclear assembly at the nuclear membrane fusion step. We propose that GAPDH plays a crucial role in the membrane fusion step in nuclear assembly in a Xenopus egg extract cell-free system. The nuclear envelope (NE)1 of eukaryotes is composed of inner and outer nuclear membranes, nuclear pore complexes, and the nuclear lamina. NE breakdown during the mitotic prophase results in the dispersal of both nuclear membranes into the mitotic endoplasmic reticulum (ER) network. Inner nuclear membrane proteins such as lamin B receptor, laminaassociated polypeptide 2, and emerin reconcentrate on the surface of decondensing chromatin during the late anaphase, and then the NE is re-formed (1, 2). These intrinsic membrane proteins and lamins are believed to play a critical role in NE reassembly (3-5). NE assembly can be studied in vitro using extracts of meiotic or mitotic cells (6, 7). The assembly requires cytosolic factors and is inhibited by a non-hydrolyzable GTP analogue, N-ethylmaleimide, and a calcium chelator, BAPTA (1,2-bis(2-aminophenoxy)ethane-N,N,NЈ,NЈ-tetraacetic acid) (8). In vitro, NE assembly is initiated by the binding of membrane vesicles to decondensed chromatin in an energy-independent manner (9 -11). Once bound to chromatin, membrane vesicles fuse and flatten. The insertion of nuclear pore complexes and the expansion of the NE require both energy and cytosolic components (12). The fusion of vesicles on chromatin is inhibited by a non-hydrolyzable GTP analogue (8, 13) and requires Ran GTPase and a regulator of chromatin condensation 1, RCC1/Ran GTP exchange factor (14 -16). Remarkably, agarose beads coated with Ran allow the assembly of a nuclear pore complex-containing NE (17, 18). After the formation of a closed NE around chromatin, further NE growth requires nucleocytoplasmic transport and further membrane fusion (8,19). Analysis of membrane fractions of a Xenopus egg extract suggested that the population of vesicles required for NE assembly is not uniform and that different membranes might be required fo...
In order to clarify the difference of clinical and pathological features between the IgA nephropathy patients with acute and insidious onset, 427 patients were examined in this study. Seventy-eight patients with acute onset (group 1) were often associated with mucosal system infections at the abrupt onset. This group revealed macroscopic hematuria, more severe microscopic hematuria (more than 20/hpf), higher glomerular filtration rate (p < 0.01) and lower serum levels of C3 (p < 0.01). It had also a significantly higher incidence of exudative lesions (p < 0.001). On the other hand, the onset of 349 patients (group 2) was noticed to be insidious without preceding infections. This group showed a more severe increase in mesangial cells (p < 0.01) and a significantly higher incidence of adhesion, arterial sclerosis and tubulointerstitial changes. Deposition of Clq, C4 and IgM and detachment of visceral epithelium from the basement membrane were more frequently seen in group 2. Twenty-seven of 345 patients followed for at least 1 year after the biopsy were on maintenance hemodialysis: 1 patient was in group 1 and 26 were in group 2. These results clarified that there was a difference in clinical, laboratory and histopathological findings between the patients with IgA nephropathy with acute and insidious onset.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.