Regulation of cell migration and behavior in Caenorhabditis elegans

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Title Regulation of cell migration and behavior in Caenorhabditis elegans
Publication Type dissertation
School or College School of Medicine
Department Oncological Sciences
Author Pickett, Christopher Lee
Date 2006-12
Description Transcription initiation is a key regulatory point of nearly every cell signaling pathway; therefore, understanding the regulation and function or transcription factors is essential for understanding physiological and pathological processes. The Myc and Mondo transcription factors heterodimerize with Max and Mlx, respectively, bind DNA, and activate transcription of many of the same promoters. Antagonizing Myc and Mondo are the Mad proteins which dimerize with either Max or Mlx to repress transcription. The regulation of Mondo subcellular localization is unique among family members as this protein localizes to the outer michondrial membrane. Mondo proteins have clear nuclear functions in regulating the transcription of key glycolytic enzymes, yet the signal(s) that cause Mondo translocation to the nucleus are not yet known. To characterize the genetic interactions of Myc superfamily members and examine the regulation of Mondo subcellular localization, we examined their orthologs in the model genetic and developmental organism, Caenorhabditis elegans. The nematode orthologs of Myc and Mondo, MML-1, and Mlx, MXL-2, heterodimerize and activate transcription similar to their mammalian counterparts. Despite a high degree of sequence conservation in subcellular localization domains, MML-1 is a nuclear protein. MML-1 and MXL-2 play roles in cell migration and behavior. These proteins act in the nonmigrating hypodermis to regulate the transcription of extracellular matrix components which control migration of ray 1 precursor cells. MML-1/MXL-2, in conjunction with Wnt/BAR-1 and semaphorin signaling, regulate the migration of ray 1 precursor cells. Further, we find that MML-1/MXL-2 regulates male attraction to hermaphrodites and antagonizes MDL-1/MXL-1 in regulating hermaphrodite avoidance. These functions of MML-1 and MXL-2 broaden the roles of Myc and Mondo proteins suggesting additional, but currently unappreciated, roles in development and disease for this highly conserved network of transcription factors.
Type Text
Publisher University of Utah
Subject MESH Caenorhabditis elegans; Transcription Factors; Transcription, Genetic; Signal Transduction; DNA-Binding Proteins; Gene Expression Regulation
Dissertation Institution University of Utah
Dissertation Name Doctor of Philosophy
Language eng
Relation is Version of Digital reproduction of Regulation of Cell Migration and Behavior in Caenorhabditis elegans. Print version available at J. Willard Marriott Library Special Collections.
Rights Management Copyright © Christopher Lee Pickett 2006
Format application/pdf
Format Medium application/pdf
Format Extent 1,830,121 bytes
Identifier undthes,3922
Source Original University of Utah Spencer S. Eccles Health Sciences Library (no longer available)
Master File Extent 1,830,178 bytes
ARK ark:/87278/s6sq9278
Setname ir_etd
ID 191754
Reference URL https://collections.lib.utah.edu/ark:/87278/s6sq9278
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