Biomedical subjects

Gwen Lomberk

Publications and source records attributed to Gwen Lomberk.

5 recordsLinked to original sources

PubMed2006

Animal models.

Research on basic mechanisms that regulate pancreatic organogenesis may help to define molecular pathways involved in the development of pancreatic diseases. In this regard, animal models have become an essential part of advancing our research efforts. There are several animal models which have been utilized specifically for normal pancreatic development and disease pathobiology. Here we highlight some important websites that serve as valuable resources for research in model organisms. In particular, websites containing information on mouse, rat, swine, zebra fish and xenopus models will be discussed due to their direct utility in pancreatic research.

Animals↗

PubMed2006

Evidence for the existence of an HP1-mediated subcode within the histone code.

Currently, the mammalian heterochromatic proteins HP1alpha, HP1beta and the pan-nuclear HP1gamma are considered 'gatekeepers' of methyl-K9-H3-mediated silencing. Understanding how the binding of these proteins to post-translationally modified histones is switched on and off will further our knowledge of how the histone code is modulated. Here, we report that all three HP1 isoforms can be extensively modified, similar to histones, suggesting that the silencing of gene expression may be further regulated beyond the histone code. To assess the potential impact of these modifications, we analysed the phosphorylation of HP1gamma at Ser 83 as a 'model modification'. We demonstrate that P-Ser 83-HP1gamma has an exclusively euchromatic localization, interacts with Ku70 (a regulatory protein involved in multiple nuclear procesess), has impaired silencing activity and serves as a marker for transcription elongation. These observations predict that regulation of silencing by methyl-K9-H3 through modification of mammalian HP1 proteins may be more complex than previously thought and suggests the existence of an HP1-mediated 'silencing subcode' that underlies the instructions of the histone code.

Acetylation↗

PubMed2006

The Heterochromatin Protein 1 family.

Heterochromatin Protein 1 (HP1) was first discovered in Drosophila as a dominant suppressor of position-effect variegation and a major component of heterochromatin. The HP1 family is evolutionarily conserved, with members in fungi, plants and animals but not prokaryotes, and there are multiple members within the same species. The amino-terminal chromodomain binds methylated lysine 9 of histone H3, causing transcriptional repression. The highly conserved carboxy-terminal chromoshadow domain enables dimerization and also serves as a docking site for proteins involved in a wide variety of nuclear functions, from transcription to nuclear architecture. In addition to heterochromatin packaging, it is becoming increasingly clear that HP1 proteins have diverse roles in the nucleus, including the regulation of euchromatic genes. HP1 proteins are amenable to posttranslational modifications that probably regulate these distinct functions, thereby creating a subcode within the context of the 'histone code' of histone posttranslational modifications.

Animals↗

PubMed2005

The family feud: turning off Sp1 by Sp1-like KLF proteins.

Sp1 is one of the best characterized transcriptional activators. The biological importance of Sp1 is underscored by the fact that several hundreds of genes are thought to be regulated by this protein. However, during the last 5 years, a more extended family of Sp1-like transcription factors has been identified and characterized by the presence of a conserved DNA-binding domain comprising three Krüppel-like zinc fingers. Each distinct family member differs in its ability to regulate transcription, and, as a consequence, to influence cellular processes. Specific activation and repression domains located within the N-terminal regions of these proteins are responsible for these differences by facilitating interactions with various co-activators and co-repressors. The present review primarily focuses on discussing the structural, biochemical and biological functions of the repressor members of this family of transcription factors. The existence of these transcriptional repressors provides a tightly regulated mechanism for silencing a large number of genes that are already known to be activated by Sp1.

Amino Acid Sequence↗

PubMed2005

When developmental signaling pathways go wrong and their impact on pancreatic cancer development.

PURPOSE OF REVIEW: To describe recent studies of developmental signal pathways and their relation to the development of pancreatic cancer. RECENT FINDINGS: Pancreatic development and its relation to pancreatic cancer remain one of the most provocative areas in the field of pancreatology. Interestingly, for a long time, investigators in this field of research worked diligently in describing pathways that were shared by both processes, hoping that the day would come when their efforts would be translated into the development of diagnostic modalities and new treatments. Fortunately, during the past 2 years, we have witnessed the development of small molecules that specifically target distinct pathways, thus providing the proof of principle that the hope of many scientists in the field of pancreatic cancer was justified. SUMMARY: This conceptual validation of previous experiments has fuelled new studies, the results of which will be the focus of this review.

Humans↗