Alexander Gann - Academia.edu (original) (raw)

Papers by Alexander Gann

Research paper thumbnail of Transcription initiation: imposing specificity by localization

Essays in biochemistry, 2001

Many crucial cellular enzymes--including RNA polymerases, kinases, phosphatases, proteases, acety... more Many crucial cellular enzymes--including RNA polymerases, kinases, phosphatases, proteases, acetylaters, etc.--have multiple potential substrates. Regulation entails substrate selection, a process effected by a mechanism we call regulated localization. This formulation is particularly well illustrated by the mechanisms of gene regulation. Analysis of these mechanisms reveals that regulated localization requires simple molecular interactions. These molecular interactions readily lend themselves to combinatorial control. This system of regulation is highly 'evolvable'. Its use accounts, at least in part, for the nature of many of the complexities observed in biological systems.

Bookmarks Related papers MentionsView impact

Research paper thumbnail of Newt Myotubes Reenter the Cell Cycle by Phosphorylation of the Retinoblastoma Protein

The Journal of Cell Biology, 1997

Bookmarks Related papers MentionsView impact

Research paper thumbnail of フランシス・クリックの手紙（上）

Nature Digest, 2011

Bookmarks Related papers MentionsView impact

Research paper thumbnail of Life illuminated : selected papers from Cold Spring Harbor : volume 2, 1972-1994

Bookmarks Related papers MentionsView impact

Research paper thumbnail of Imposing specificity on kinases

Science, 2003

The mitogen-activated protein kinase (MAPK) signaling cascades transmit signals from the cell sur... more The mitogen-activated protein kinase (MAPK) signaling cascades transmit signals from the cell surface to its interior. There are at least four MAPK cascades in yeast, and in response to a specific extracellular signal (different in each case), one of these cascades “fires.” Each cascade ...

Bookmarks Related papers MentionsView impact

Research paper thumbnail of Genes and signals

Bookmarks Related papers MentionsView impact

Research paper thumbnail of Towards a molecular understanding of regeneration

Trends Genet, 1996

Tanaka, Elly and Gann, Alexander (1996) Towards a molecular understanding of regeneration : 15th ... more Tanaka, Elly and Gann, Alexander (1996) Towards a molecular understanding of regeneration : 15th Singer Symposium on Models of Regeneration: Lower versus Higher Vertebrates, Institute of Child Health, London, UK, 21–22 March 1996. Trends in Genetics, 12 (7). p. 278. ISSN ...

Bookmarks Related papers MentionsView impact

Research paper thumbnail of The annotated and illustrated double helix

Bookmarks Related papers MentionsView impact

Research paper thumbnail of Conservation of complex DNA recognition domains between families of restriction enzymes

Cell, Jan 13, 1989

Bookmarks Related papers MentionsView impact

Research paper thumbnail of Newt myotubes reenter the cell cycle by phosphorylation of the retinoblastoma protein

The Journal of cell biology, Jan 13, 1997

Withdrawal from the cell cycle is an essential aspect of vertebrate muscle differentiation and re... more Withdrawal from the cell cycle is an essential aspect of vertebrate muscle differentiation and requires the retinoblastoma (Rb) protein that inhibits expression of genes needed for cell cycle entry. It was shown recently that cultured myotubes derived from the Rb-/- mouse reenter the cell cycle after serum stimulation (Schneider, J.W., W. Gu, L. Zhu, V. Mahdavi, and B. Nadal-Ginard. 1994. Science (Wash. DC). 264:1467-1471). In contrast with other vertebrates, adult urodele amphibians such as the newt can regenerate their limbs, a process involving cell cycle reentry and local reversal of differentiation. Here we show that myotubes formed in culture from newt limb cells are refractory to several growth factors, but they undergo S phase after serum stimulation and accumulate 4N nuclei. This response to serum is inhibited by contact with mononucleate cells. Despite the phenotypic parallel with Rb-/- mouse myotubes, Rb is expressed in the newt myotubes, and its phosphorylation via cycli...

Bookmarks Related papers MentionsView impact

Research paper thumbnail of Indications for Iridectomy and Sclerotomy in Glaucoma

Bookmarks Related papers MentionsView impact

Research paper thumbnail of Round the World

Bookmarks Related papers MentionsView impact

Research paper thumbnail of Noreen Elizabeth Murray CBE. 26 February 1935 -- 12 May 2011

Biographical Memoirs of Fellows of the Royal Society, 2014

Bookmarks Related papers MentionsView impact

Research paper thumbnail of Activators and targets

Nature, 1990

Proteins that activate genes are quite disparate in character; in particular, some work '... more Proteins that activate genes are quite disparate in character; in particular, some work 'universally' and others do not. A simple model can accommodate most of the recently published results.

Bookmarks Related papers MentionsView impact

Research paper thumbnail of Abortive Infection by Bacteriophage Mel of Escherichia coil K12 Strains Bearing the Plasmid CoW, I-K94

SUMMARY Bacteriophage Mel is unable to grow on Escherichia coil strains harbouring the ColV,I-K94... more SUMMARY Bacteriophage Mel is unable to grow on Escherichia coil strains harbouring the ColV,I-K94 plasmid. The nature of this inhibition was investigated, and it was found not to be due to restriction, superinfection exclusion or receptor-mediated resistance, but to be a new example of plasmid-mediated abortive infection. Investigation of events occurring during abortive Mel infection revealed some differences from previously described cases, especially with regard to late protein synthe:is, which did occur, albeit showing abnormal amounts of some proteins. No major differences were observed in membrane permeability of productively and abortively infected cells. Phage-directed DNA synthesis was reduced in abortively infected cells. Comparative studies of Mel and T4 revealed a striking similarity despite some minor differences.

Bookmarks Related papers MentionsView impact

Research paper thumbnail of Towards a molecular understanding of regeneration

Trends in Genetics, 1996

Tanaka, Elly and Gann, Alexander (1996) Towards a molecular understanding of regeneration : 15th ... more Tanaka, Elly and Gann, Alexander (1996) Towards a molecular understanding of regeneration : 15th Singer Symposium on Models of Regeneration: Lower versus Higher Vertebrates, Institute of Child Health, London, UK, 21–22 March 1996. Trends in Genetics, 12 (7). p. 278. ISSN ...

Bookmarks Related papers MentionsView impact

Research paper thumbnail of Life Illuminated: Selected Papers from Cold Spring Harbor, Volume 2, 1972–1994

The Quarterly Review of Biology, 2009

Bookmarks Related papers MentionsView impact

Research paper thumbnail of SIGNAL TRANSDUCTION: Imposing Specificity on Kinases

Science, 2003

Bookmarks Related papers MentionsView impact

Research paper thumbnail of Expression and Activity of the Newt Msx-1 Gene in Relation to Limb Regeneration

Proceedings of the Royal Society B: Biological Sciences, 1995

The Msx-1 homeobox gene is expressed in various contexts during vertebrate development, including... more The Msx-1 homeobox gene is expressed in various contexts during vertebrate development, including the progress zone of the avian and mouse limb bud. Expression of mouse Msx-1 in a cultured myogenic cell line conferred a transformed phenotype and inhibited fusion into myotubes. It has been proposed that Msx-1 expression is required to maintain certain cells in a proliferating and undifferentiated state and may be associated with the ability to regenerate limbs. Urodele amphibians such as the newt regenerate their limbs by formation of a growth zone or blastema, and we have isolated and sequenced newt Msx-1 (NvMsx-1) from a limb blastemal cDNA library. NvMsx-1 expression was detectable in RNA preparations from both limb and tail and their regeneration blastemas, although cultured cells established from limb blastemal mesenchyme gave negative results. When either COS cells or cultured newt blastemal cells were cotransfected with an expression vector for NvMsx-1 and reporter plasmids containing multiple homeobox protein binding sites, NvMsx-1 repressed reporter expression. If NvMsx-1 was expressed together with a marker enzyme in cultured newt blastemal cells, no significant difference in DNA synthesis was observed relative to control transfectants. When myogenic mononucleate cells were transfected with NvMsx-1 and subsequently exposed to low serum to promote fusion, the fraction of Msx-1 positive cells in myotubes was comparable to a control transfected population analysed in the same culture. These results indicate that although Msx-1 expression could be important for limb regeneration, it does not exert a cell-autonomous effect on proliferation or myogenic differentiation of cultured blastemal cells.

Bookmarks Related papers MentionsView impact

Research paper thumbnail of Receptor Isoform Specificity in a Cellular Response to Retinoic Acid

Proceedings of the Royal Society B: Biological Sciences, 1996

The effects of retinoic acid on cell proliferation, differentiation and patterning are thought to... more The effects of retinoic acid on cell proliferation, differentiation and patterning are thought to be mediated by the various retinoic acid receptors. Different receptor types are encoded by distinct genes (alpha, beta, and gamma), whereas various isoforms within each type are encoded by splicing variants resulting from the use of alternative promoters. The only region that differs between isoforms is the N-terminal A region containing a transcriptional activating domain. It has been proposed that these alternative A regions confer distinct activities on the receptors, thus allowing each to mediate specific effects of retinoic acid, but it has been difficult to demonstrate such isoform specificity as most cells express a number of different retinoic acid receptors. In an attempt to test whether different isoforms can mediate distinct biological effects we are focusing on retinoic-acid-dependent growth inhibition of newt limb cells. We have constructed chimaeric receptors in which the retinoic acid binding domain of each of five newt retinoic acid receptors has been replaced with a thyroid hormone (T3) binding domain. These constructs were introduced individually into cells whose growth rate was then measured in the presence of T3. The chimaeric alpha 1 receptor mediated T3-dependent inhibition of proliferation that was comparable to that given by retinoic acid, whereas the alpha 2 isoform had no activity in this assay, nor did the delta 1A, delta 1B and Delta 2 receptors. When the A region was deleted from the alpha 1 chimaera it remained a potent T3-dependent transcriptional activator, but no longer mediated T3-dependent growth inhibition. In contrast, when the A region of alpha 1 was transferred to a delta chimaeric receptor, the resulting molecule was fully active in T3-dependent growth inhibition. This is the first direct evidence for isoform specificity in a biological response to retinoic acid, and demonstrates that the specificity of this response is confined to the A region.

Bookmarks Related papers MentionsView impact

Research paper thumbnail of Transcription initiation: imposing specificity by localization

Essays in biochemistry, 2001

Many crucial cellular enzymes--including RNA polymerases, kinases, phosphatases, proteases, acety... more Many crucial cellular enzymes--including RNA polymerases, kinases, phosphatases, proteases, acetylaters, etc.--have multiple potential substrates. Regulation entails substrate selection, a process effected by a mechanism we call regulated localization. This formulation is particularly well illustrated by the mechanisms of gene regulation. Analysis of these mechanisms reveals that regulated localization requires simple molecular interactions. These molecular interactions readily lend themselves to combinatorial control. This system of regulation is highly 'evolvable'. Its use accounts, at least in part, for the nature of many of the complexities observed in biological systems.

Bookmarks Related papers MentionsView impact

Research paper thumbnail of Newt Myotubes Reenter the Cell Cycle by Phosphorylation of the Retinoblastoma Protein

The Journal of Cell Biology, 1997

Bookmarks Related papers MentionsView impact

Research paper thumbnail of フランシス・クリックの手紙（上）

Nature Digest, 2011

Bookmarks Related papers MentionsView impact

Research paper thumbnail of Life illuminated : selected papers from Cold Spring Harbor : volume 2, 1972-1994

Bookmarks Related papers MentionsView impact

Research paper thumbnail of Imposing specificity on kinases

Science, 2003

The mitogen-activated protein kinase (MAPK) signaling cascades transmit signals from the cell sur... more The mitogen-activated protein kinase (MAPK) signaling cascades transmit signals from the cell surface to its interior. There are at least four MAPK cascades in yeast, and in response to a specific extracellular signal (different in each case), one of these cascades “fires.” Each cascade ...

Bookmarks Related papers MentionsView impact

Research paper thumbnail of Genes and signals

Bookmarks Related papers MentionsView impact

Research paper thumbnail of Towards a molecular understanding of regeneration

Trends Genet, 1996

Tanaka, Elly and Gann, Alexander (1996) Towards a molecular understanding of regeneration : 15th ... more Tanaka, Elly and Gann, Alexander (1996) Towards a molecular understanding of regeneration : 15th Singer Symposium on Models of Regeneration: Lower versus Higher Vertebrates, Institute of Child Health, London, UK, 21–22 March 1996. Trends in Genetics, 12 (7). p. 278. ISSN ...

Bookmarks Related papers MentionsView impact

Research paper thumbnail of The annotated and illustrated double helix

Bookmarks Related papers MentionsView impact

Research paper thumbnail of Conservation of complex DNA recognition domains between families of restriction enzymes

Cell, Jan 13, 1989

Bookmarks Related papers MentionsView impact

Research paper thumbnail of Newt myotubes reenter the cell cycle by phosphorylation of the retinoblastoma protein

The Journal of cell biology, Jan 13, 1997

Withdrawal from the cell cycle is an essential aspect of vertebrate muscle differentiation and re... more Withdrawal from the cell cycle is an essential aspect of vertebrate muscle differentiation and requires the retinoblastoma (Rb) protein that inhibits expression of genes needed for cell cycle entry. It was shown recently that cultured myotubes derived from the Rb-/- mouse reenter the cell cycle after serum stimulation (Schneider, J.W., W. Gu, L. Zhu, V. Mahdavi, and B. Nadal-Ginard. 1994. Science (Wash. DC). 264:1467-1471). In contrast with other vertebrates, adult urodele amphibians such as the newt can regenerate their limbs, a process involving cell cycle reentry and local reversal of differentiation. Here we show that myotubes formed in culture from newt limb cells are refractory to several growth factors, but they undergo S phase after serum stimulation and accumulate 4N nuclei. This response to serum is inhibited by contact with mononucleate cells. Despite the phenotypic parallel with Rb-/- mouse myotubes, Rb is expressed in the newt myotubes, and its phosphorylation via cycli...

Bookmarks Related papers MentionsView impact

Research paper thumbnail of Indications for Iridectomy and Sclerotomy in Glaucoma

Bookmarks Related papers MentionsView impact

Research paper thumbnail of Round the World

Bookmarks Related papers MentionsView impact

Research paper thumbnail of Noreen Elizabeth Murray CBE. 26 February 1935 -- 12 May 2011

Biographical Memoirs of Fellows of the Royal Society, 2014

Bookmarks Related papers MentionsView impact

Research paper thumbnail of Activators and targets

Nature, 1990

Proteins that activate genes are quite disparate in character; in particular, some work '... more Proteins that activate genes are quite disparate in character; in particular, some work 'universally' and others do not. A simple model can accommodate most of the recently published results.

Bookmarks Related papers MentionsView impact

Research paper thumbnail of Abortive Infection by Bacteriophage Mel of Escherichia coil K12 Strains Bearing the Plasmid CoW, I-K94

SUMMARY Bacteriophage Mel is unable to grow on Escherichia coil strains harbouring the ColV,I-K94... more SUMMARY Bacteriophage Mel is unable to grow on Escherichia coil strains harbouring the ColV,I-K94 plasmid. The nature of this inhibition was investigated, and it was found not to be due to restriction, superinfection exclusion or receptor-mediated resistance, but to be a new example of plasmid-mediated abortive infection. Investigation of events occurring during abortive Mel infection revealed some differences from previously described cases, especially with regard to late protein synthe:is, which did occur, albeit showing abnormal amounts of some proteins. No major differences were observed in membrane permeability of productively and abortively infected cells. Phage-directed DNA synthesis was reduced in abortively infected cells. Comparative studies of Mel and T4 revealed a striking similarity despite some minor differences.

Bookmarks Related papers MentionsView impact

Research paper thumbnail of Towards a molecular understanding of regeneration

Trends in Genetics, 1996

Tanaka, Elly and Gann, Alexander (1996) Towards a molecular understanding of regeneration : 15th ... more Tanaka, Elly and Gann, Alexander (1996) Towards a molecular understanding of regeneration : 15th Singer Symposium on Models of Regeneration: Lower versus Higher Vertebrates, Institute of Child Health, London, UK, 21–22 March 1996. Trends in Genetics, 12 (7). p. 278. ISSN ...

Bookmarks Related papers MentionsView impact

Research paper thumbnail of Life Illuminated: Selected Papers from Cold Spring Harbor, Volume 2, 1972–1994

The Quarterly Review of Biology, 2009

Bookmarks Related papers MentionsView impact

Research paper thumbnail of SIGNAL TRANSDUCTION: Imposing Specificity on Kinases

Science, 2003

Bookmarks Related papers MentionsView impact

Research paper thumbnail of Expression and Activity of the Newt Msx-1 Gene in Relation to Limb Regeneration

Proceedings of the Royal Society B: Biological Sciences, 1995

The Msx-1 homeobox gene is expressed in various contexts during vertebrate development, including... more The Msx-1 homeobox gene is expressed in various contexts during vertebrate development, including the progress zone of the avian and mouse limb bud. Expression of mouse Msx-1 in a cultured myogenic cell line conferred a transformed phenotype and inhibited fusion into myotubes. It has been proposed that Msx-1 expression is required to maintain certain cells in a proliferating and undifferentiated state and may be associated with the ability to regenerate limbs. Urodele amphibians such as the newt regenerate their limbs by formation of a growth zone or blastema, and we have isolated and sequenced newt Msx-1 (NvMsx-1) from a limb blastemal cDNA library. NvMsx-1 expression was detectable in RNA preparations from both limb and tail and their regeneration blastemas, although cultured cells established from limb blastemal mesenchyme gave negative results. When either COS cells or cultured newt blastemal cells were cotransfected with an expression vector for NvMsx-1 and reporter plasmids containing multiple homeobox protein binding sites, NvMsx-1 repressed reporter expression. If NvMsx-1 was expressed together with a marker enzyme in cultured newt blastemal cells, no significant difference in DNA synthesis was observed relative to control transfectants. When myogenic mononucleate cells were transfected with NvMsx-1 and subsequently exposed to low serum to promote fusion, the fraction of Msx-1 positive cells in myotubes was comparable to a control transfected population analysed in the same culture. These results indicate that although Msx-1 expression could be important for limb regeneration, it does not exert a cell-autonomous effect on proliferation or myogenic differentiation of cultured blastemal cells.

Bookmarks Related papers MentionsView impact

Research paper thumbnail of Receptor Isoform Specificity in a Cellular Response to Retinoic Acid

Proceedings of the Royal Society B: Biological Sciences, 1996

The effects of retinoic acid on cell proliferation, differentiation and patterning are thought to... more The effects of retinoic acid on cell proliferation, differentiation and patterning are thought to be mediated by the various retinoic acid receptors. Different receptor types are encoded by distinct genes (alpha, beta, and gamma), whereas various isoforms within each type are encoded by splicing variants resulting from the use of alternative promoters. The only region that differs between isoforms is the N-terminal A region containing a transcriptional activating domain. It has been proposed that these alternative A regions confer distinct activities on the receptors, thus allowing each to mediate specific effects of retinoic acid, but it has been difficult to demonstrate such isoform specificity as most cells express a number of different retinoic acid receptors. In an attempt to test whether different isoforms can mediate distinct biological effects we are focusing on retinoic-acid-dependent growth inhibition of newt limb cells. We have constructed chimaeric receptors in which the retinoic acid binding domain of each of five newt retinoic acid receptors has been replaced with a thyroid hormone (T3) binding domain. These constructs were introduced individually into cells whose growth rate was then measured in the presence of T3. The chimaeric alpha 1 receptor mediated T3-dependent inhibition of proliferation that was comparable to that given by retinoic acid, whereas the alpha 2 isoform had no activity in this assay, nor did the delta 1A, delta 1B and Delta 2 receptors. When the A region was deleted from the alpha 1 chimaera it remained a potent T3-dependent transcriptional activator, but no longer mediated T3-dependent growth inhibition. In contrast, when the A region of alpha 1 was transferred to a delta chimaeric receptor, the resulting molecule was fully active in T3-dependent growth inhibition. This is the first direct evidence for isoform specificity in a biological response to retinoic acid, and demonstrates that the specificity of this response is confined to the A region.

Bookmarks Related papers MentionsView impact