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University of Massachusetts Medical School Faculty Publications

Molecular Genetics

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Articles 1 - 7 of 7

Full-Text Articles in Cell Biology

Genetic Models Of Apoptosis-Induced Proliferation Decipher Activation Of Jnk And Identify A Requirement Of Egfr Signaling For Tissue Regenerative Responses In Drosophila, Yun Fan, Shiuan Wang, Jacob Hernandez, Vildan Betul Yenigun, Gillian Hertlein, Caitlin E. Fogarty, Jillian L. Lindblad, Andreas Bergmann Jan 2014

Genetic Models Of Apoptosis-Induced Proliferation Decipher Activation Of Jnk And Identify A Requirement Of Egfr Signaling For Tissue Regenerative Responses In Drosophila, Yun Fan, Shiuan Wang, Jacob Hernandez, Vildan Betul Yenigun, Gillian Hertlein, Caitlin E. Fogarty, Jillian L. Lindblad, Andreas Bergmann

University of Massachusetts Medical School Faculty Publications

Recent work in several model organisms has revealed that apoptotic cells are able to stimulate neighboring surviving cells to undergo additional proliferation, a phenomenon termed apoptosis-induced proliferation. This process depends critically on apoptotic caspases such as Dronc, the Caspase-9 ortholog in Drosophila, and may have important implications for tumorigenesis. While it is known that Dronc can induce the activity of Jun N-terminal kinase (JNK) for apoptosis-induced proliferation, the mechanistic details of this activation are largely unknown. It is also controversial if JNK activity occurs in dying or in surviving cells. Signaling molecules of the Wnt and BMP families have been ...


Immortalized Myogenic Cells From Congenital Muscular Dystrophy Type1a Patients Recapitulate Aberrant Caspase Activation In Pathogenesis: A New Tool For Mdc1a Research, Soonsang Yoon, Guido Stadler, Mary Lou Beermann, Eric V. Schmidt, James A. Windelborn, Peter Schneiderat, Woodring E. Wright, Jeffrey Boone Miller Dec 2013

Immortalized Myogenic Cells From Congenital Muscular Dystrophy Type1a Patients Recapitulate Aberrant Caspase Activation In Pathogenesis: A New Tool For Mdc1a Research, Soonsang Yoon, Guido Stadler, Mary Lou Beermann, Eric V. Schmidt, James A. Windelborn, Peter Schneiderat, Woodring E. Wright, Jeffrey Boone Miller

University of Massachusetts Medical School Faculty Publications

BACKGROUND: Congenital muscular dystrophy Type 1A (MDC1A) is a severe, recessive disease of childhood onset that is caused by mutations in the LAMA2 gene encoding laminin-alpha2. Studies with both mouse models and primary cultures of human MDC1A myogenic cells suggest that aberrant activation of cell death is a significant contributor to pathogenesis in laminin-alpha2-deficiency.

METHODS: To overcome the limited population doublings of primary cultures, we generated immortalized, clonal lines of human MDC1A myogenic cells via overexpression of both CDK4 and the telomerase catalytic component (human telomerase reverse transcriptase (hTERT)).

RESULTS: The immortalized MDC1A myogenic cells proliferated indefinitely when cultured at ...


The Dna Damage And The Dna Replication Checkpoints Converge At The Mbf Transcription Factor, Tsvetomira Ivanova, Isabel Alves-Rodrigues, Blanca Gomez-Escoda, Chaitali Dutta, James A. Decaprio, Nicholas R. Rhind, Elena Hidalgo, Jose Ayte Nov 2013

The Dna Damage And The Dna Replication Checkpoints Converge At The Mbf Transcription Factor, Tsvetomira Ivanova, Isabel Alves-Rodrigues, Blanca Gomez-Escoda, Chaitali Dutta, James A. Decaprio, Nicholas R. Rhind, Elena Hidalgo, Jose Ayte

University of Massachusetts Medical School Faculty Publications

In fission yeast cells, Cds1 is the effector kinase of the DNA replication checkpoint. We previously showed that when the DNA replication checkpoint is activated, the repressor Yox1 is phosphorylated and inactivated by Cds1, resulting in activation of MluI-binding factor (MBF)-dependent transcription. This is essential to reinitiate DNA synthesis and for correct G1-to-S transition. Here we show that Cdc10, which is an essential part of the MBF core, is the target of the DNA damage checkpoint. When fission yeast cells are treated with DNA-damaging agents, Chk1 is activated and phosphorylates Cdc10 at its carboxy-terminal domain. This modification is responsible ...


Phosphorylation Of Centromeric Histone H3 Variant Regulates Chromosome Segregation In S. Cerevisiae, Lars Boeckmann, Yoshimitsu Takahashi, Wei-Chun Au, Prashant K. Mishra, John S. Choy, Anthony R. Dawson, May Y. Szeto, Timothy J. Waybright, Christopher Heger, Christopher Mcandrew, Paul K. Goldsmith, Timothy D. Veenstra, Richard E. Baker, Munira A. Basrai Jun 2013

Phosphorylation Of Centromeric Histone H3 Variant Regulates Chromosome Segregation In S. Cerevisiae, Lars Boeckmann, Yoshimitsu Takahashi, Wei-Chun Au, Prashant K. Mishra, John S. Choy, Anthony R. Dawson, May Y. Szeto, Timothy J. Waybright, Christopher Heger, Christopher Mcandrew, Paul K. Goldsmith, Timothy D. Veenstra, Richard E. Baker, Munira A. Basrai

University of Massachusetts Medical School Faculty Publications

The centromeric histone H3 variant (CenH3) is essential for chromosome segregation in eukaryotes. We have identified posttranslational modifications of S. cerevisiae CenH3, Cse4. Functional characterization of cse4 phosphorylation mutants showed growth and chromosome segregation defects when combined with kinetochore mutants okp1 and ame1. Using a phosphoserine-specific antibody we showed that the association of phosphorylated Cse4 with centromeres is increased in response to defective microtubule attachment or reduced cohesion. We determined that evolutionarily conserved Ipl1/Aurora B contributes to phosphorylation of Cse4, as levels of phosphorylated Cse4 were reduced at centromeres in ipl1 strains in vivo and in vitro assays showed ...


Wnt And Cdk-1 Regulate Cortical Release Of Wrm-1/Beta-Catenin To Control Cell Division Orientation In Early Caenorhabditis Elegans Embryos, Soyoung Kim, Takao Ishidate, Rita Sharma, Martha C. Soto, Darryl Conte Jr., Craig C. Mello, Masaki Shirayama Feb 2013

Wnt And Cdk-1 Regulate Cortical Release Of Wrm-1/Beta-Catenin To Control Cell Division Orientation In Early Caenorhabditis Elegans Embryos, Soyoung Kim, Takao Ishidate, Rita Sharma, Martha C. Soto, Darryl Conte Jr., Craig C. Mello, Masaki Shirayama

University of Massachusetts Medical School Faculty Publications

In early Caenorhabditis elegans embryos, the Wingless/int (Wnt)- and Src-signaling pathways function in parallel to induce both the division orientation of the endomesoderm (EMS) blastomere and the endoderm fate of the posterior EMS daughter cell, called E. Here, we show that, in addition to its role in endoderm specification, the beta-catenin-related protein Worm armadillo 1 (WRM-1) also plays a role in controlling EMS division orientation. WRM-1 localizes to the cortex of cells in both embryos and larvae and is released from the cortex in a Wnt-responsive manner. We show that WRM-1 cortical release is disrupted in a hypomorphic cyclin-dependent ...


Identification Of Map4k4 As A Novel Suppressor Of Skeletal Muscle Differentiation, Mengxi Wang, Shinya U. Amano, Rachel J. Roth Flach, Anil Chawla, Myriam Aouadi, Michael P. Czech Feb 2013

Identification Of Map4k4 As A Novel Suppressor Of Skeletal Muscle Differentiation, Mengxi Wang, Shinya U. Amano, Rachel J. Roth Flach, Anil Chawla, Myriam Aouadi, Michael P. Czech

University of Massachusetts Medical School Faculty Publications

Myoblast differentiation into mature myotubes is a critical step in the development and repair of human skeletal muscle. Here we show that small interfering RNA (siRNA)-based silencing of the Ste20-like mitogen-activated protein 4 kinase 4 (Map4k4) in C2C12 myoblasts markedly enhances expression of myogenic differentiation genes, myoblast fusion, and myotube diameter. In contrast, adenovirus-mediated expression of native Map4k4 in C2C12 cells attenuates each of these processes, indicating that Map4k4 is a negative regulator of myogenic differentiation and hypertrophy. Expression of a Map4k4 kinase-inactive mutant enhances myotube formation, suggesting that the kinase activity of Map4k4 is essential for its inhibition ...


An Unusual Two-Step Control Of Cpeb Destruction By Pin1, Morris Nechama, Chien-Ling Lin, Joel D. Richter Jan 2013

An Unusual Two-Step Control Of Cpeb Destruction By Pin1, Morris Nechama, Chien-Ling Lin, Joel D. Richter

University of Massachusetts Medical School Faculty Publications

Cytoplasmic polyadenylation is a conserved mechanism that controls mRNA translation and stability. A key protein that promotes polyadenylation-induced translation of mRNAs in maturing Xenopus oocytes is the cytoplasmic polyadenylation element binding protein (CPEB). During this meiotic transition, CPEB is subjected to phosphorylation-dependent ubiquitination and partial destruction, which is necessary for successive waves of polyadenylation of distinct mRNAs. Here we identify the peptidyl-prolyl cis-trans isomerase Pin1 as an important factor mediating CPEB destruction. Pin1 interacts with CPEB in an unusual manner in which it occurs prior to CPEB phosphorylation and prior to Pin1 activation by serine 71 dephosphorylation. Upon induction of ...