Robert D Goldman

..In light of our findings that WFA affects multiple IF systems, which are expressed in many tissues of the body, caution is warranted in its use as an anti-cancer agent, since it may have debilitating organism-wide effects...

..Many of our advances in understanding IF are based on conversations with Ueli which have taken place during adventurous and sometimes dangerous hiking and biking trips throughout the world...

..This suggests that there are different factors regulating the dynamic properties of different types of IFs within the same cytoplasmic regions...

..IF also play a role in the organization of organelles by modulating their motility and providing anchorage sites within the cytoplasm...

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..These findings demonstrate an antagonistic relationship between VIF and the formation of lamellipodia...

..The study also emphasizes the importance of lamins in nuclear assembly and chromatin organization...

..These findings also provide insights into the mechanisms underlying the numerous disease-causing mutations located within the lamin Ig-fold...

..This overexpression eventually leads to cell cycle arrest at the G1/S boundary. These results demonstrate the importance of LB1 in regulating the proliferation and senescence of human diploid cells through a ROS signaling pathway...

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..These results provide insights into the mechanisms responsible for premature aging and also shed light on the role of lamins in the normal process of human aging...

..The epigenetic changes described most likely represent molecular mechanisms responsible for the rapid progression of premature aging in HGPS patients...

..These differences require an intact vimentin network. Therefore, vimentin IF recruitment to the cell surface is tightly regulated and modulates the strength of adhesion of cells to their substrate...

..The recent findings that IF and their precursors are frequently associated with signaling molecules have revealed new functions for IF beyond their more traditional roles as mechanical integrators of cells and tissues...

..We suggest that keratin particles constitute a reservoir of protein that can be recruited into KIFs under flow, creating a more robust cytoskeleton able to withstand shear forces more effectively...

..These differences in motility may be related to their interactions with different types of molecular motor and/or other factors, such as IF-associated proteins...

..Our evidence suggests that the organization and regulation of chromatin are influenced by interconnections between these lamin microdomains...

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..In addition, we discuss recent evidence supporting the importance of lamins in viral infections...

..They may also regulate chromatin functions by interacting with factors that epigenetically modify the chromatin or directly regulate replication or transcription...

..Importantly, these data provided clues regarding a molecular link between mechanically induced signal transduction and alterations in cytoskeletal IF...

..On the basis of these observations, we speculate that nestin may play a role in the trafficking and distribution of IF proteins and potentially other cellular factors to daughter cells during progenitor cell division...

..These data suggest that shear stress promotes the disassembly and degradation of the keratin IF network via phosphorylation and the ubiquitin-proteasome pathway...

..Taken together, our data demonstrate that the nestin-mediated disassembly of vimentin IFs generates a structure capable of sequestering and modulating the activity of IDE...

..Our results demonstrate that VIFs play a predominant role in the changes in shape, adhesion, and motility that occur during the EMT...

..The results show that the motility and targeting of peripherin mRNPs, their translational control, and the assembly of an IF cytoskeletal system are linked together in a process we have termed dynamic cotranslation...

..These mutations are also providing important new insights into nuclear-cytoplasmic interactions...

..This review considers the functional implications of the motile properties of IFs and discusses the potential relationships between malfunctions in these motile activities and human diseases...

..Furthermore, the results of these experiments demonstrate that peripherin IF are critical determinants of the overall shape and architecture of neurons...

..Our data demonstrate that peripherin particles and squiggles can move as components of a rapid transport system capable of delivering cytoskeletal subunits to the most distal regions of neurites over relatively short time periods...

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..We summarize these recent findings, focusing on data from mice and humans, and highlight the expanding knowledge of these proteins in both healthy and diseased cells...

..This range of activities might help to explain why genetic defects in some of the nucleoskeletal proteins contribute to an ever-expanding list of human diseases...

..These results suggest a role for importin alpha in regulating lamin assembly and possibly modulating the interactions of lamins with lamin-binding proteins...

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..Recent studies have revealed that intermediate filaments and their associated proteins are important components in mediating this crosstalk...

..Together, our studies link the control of Ub clearance with IDE...

..As SV40 serves as a paradigm for the pathogenic human BK, JC and Merkel cell polyomavirus, this study suggests nuclear entry as a novel drug target for these infections...

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..Furthermore, these motors are to a large extent responsible for the long recognized relationships between vimentin IFs and MTs...

..We propose that integrins are mobile within the confines of focal contacts and that this mobility is supported by an actin-associated molecular motor...

..Furthermore, immunofluorescence observations indicate that this selective inhibition of polymerase II-dependent transcription involves the TATA binding protein, a component of the basal transcription factor TFIID...

..These findings suggest that Cdk5-p35 activity regulates normal NF distribution and that overexpression of Cdk5-p35 induces perikaryal accumulation of phosphorylated-NFs similar to those observed under pathological conditions...

..Taken together, our results suggest that elevated phosphorylation regulates IF assembly in vivo by changing the equilibrium constant of subunit exchange towards a higher off-rate...

..We propose that lamin B is a structural component of the long-sought-after spindle matrix that promotes microtubule assembly and organization in mitosis...

..Our data imply that nestin is a survival determinant whose action is based upon a novel mode of Cdk5 regulation, affecting the targeting, activity, and turnover of the Cdk5/p35 signaling complex...

..We observed 35-nm myosin V steps in melanophores containing no IFs. We find that myosin V steps occur faster in the absence of IFs, indicating that the IF network physically hinders organelle transport...

..These diseases, collectively termed laminopathies, affect muscle, adipose, bone, nerve and skin cells and range from muscular dystrophies to accelerated aging...

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..The high storage modulus of the KIF network, coupled with its solid-like rheological behavior, supports the role of KIF as an intracellular structural scaffold that helps epithelial cells to withstand external mechanical forces...

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..These collective studies will provide important insights into how hLA mutations cause the defects seen in progeria. ..

..In addition, attempts will be made to identify the specific binding partners, which link the A and B-type lamins to the RNA polymerase II machinery and to the DNA replication elongation complex. ..

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..The latter include the formation of Mallory bodies in alcoholic liver disease and Lewy bodies in Parkinson's disease. ..

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..Progress in this area is particularly important since mutations in nuclear lamins cause a variety of diseases including muscular dystrophies, lipodystrophies, cardiomyopathies, and premature aging syndromes. ..

..Progress in this area is particularly important since mutations in nuclear lamins cause a variety of diseases including muscular dystrophies, lipodystrophies, cardiomyopathies, and premature aging syndromes. ..

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..With regard to disease processes, this system is frequently found in an altered state in many diseases including cancer, Alzheimers disease, liver diseases and several other neurological disorders...