University of Iowa

About: University of Iowa is a education organization based out in Iowa City, Iowa, United States. It is known for research contribution in the topics: Population & Poison control. The organization has 49229 authors who have published 109171 publications receiving 5021465 citations. The organization is also known as: UI & The University of Iowa.

P-TEFb, a cyclin-dependent kinase controlling elongation by RNA polymerase II.

Abstract: The elongation phase of transcription by RNA polymerase II is one of the many steps during the generation of mature mRNAs that is subject to regulation. Shortly after initiation, RNA polymerase II comes under the control of negative transcription elongation factors, generally termed N-TEFs, and enters abortive elongation (51). During this postinitiation process, only short transcripts are generated that may be prematurely terminated. These short transcripts arise from transcription of many genes, including c-myb, c-myc, c-fos, HSP70, and the human immunodeficiency virus (HIV) long terminal repeat (LTR), and are normally subject to rapid degradation (3, 63). Escape from the action of N-TEF requires the action of at least one positive transcription elongation factor (P-TEF), eventually identified as P-TEFb (52). P-TEFb allows the transition into productive elongation, producing long transcripts from which mRNAs are derived. In this way, the fraction of initiating RNA polymerase II molecules that produce full-length transcripts is controlled by a selection process that occurs early in the elongation phase of the transcription cycle. After the transition is made into productive elongation, the efficiency of elongation may be influenced by additional factors, including S-II, TFIIF, ELL, and elongin (62, 65).

Biogenesis and Function of Multivesicular Bodies

Abstract: The two major cellular sites for membrane protein degradation are the proteasome and the lysosome. Ubiquitin attachment is a sorting signal for both degradation routes. For lysosomal degradation, ubiquitination triggers the sorting of cargo proteins into the lumen of late endosomal multivesicular bodies (MVBs)/endosomes. MVB formation occurs when a portion of the limiting membrane of an endosome invaginates and buds into its own lumen. Intralumenal vesicles are degraded when MVBs fuse to lysosomes. The proper delivery of proteins to the MVB interior relies on specific ubiquitination of cargo, recognition and sorting of ubiquitinated cargo to endosomal subdomains, and the formation and scission of cargo-filled intralumenal vesicles. Over the past five years, a number of proteins that may directly participate in these aspects of MVB function and biogenesis have been identified. However, major questions remain as to exactly what these proteins do at the molecular level and how they may accomplish these tasks.

Interaction with the NMDA receptor locks CaMKII in an active conformation

Abstract: Calcium- and calmodulin-dependent protein kinase II (CaMKII) and glutamate receptors are integrally involved in forms of synaptic plasticity that may underlie learning and memory. In the simplest model for long-term potentiation, CaMKII is activated by Ca2+ influx through NMDA (N-methyl-D-aspartate) receptors and then potentiates synaptic efficacy by inducing synaptic insertion and increased single-channel conductance of AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid) receptors. Here we show that regulated CaMKII interaction with two sites on the NMDA receptor subunit NR2B provides a mechanism for the glutamate-induced translocation of the kinase to the synapse in hippocampal neurons. This interaction can lead to additional forms of potentiation by: facilitated CaMKII response to synaptic Ca2+; suppression of inhibitory autophosphorylation of CaMKII; and, most notably, direct generation of sustained Ca2+/calmodulin (CaM)-independent (autonomous) kinase activity by a mechanism that is independent of the phosphorylation state. Furthermore, the interaction leads to trapping of CaM that may reduce down-regulation of NMDA receptor activity. CaMKII-NR2B interaction may be prototypical for direct activation of a kinase by its targeting protein.