The Glutamine-Alanine Repeat Domain of TCERG1 is Required for the Inhibition of the Growth Arrest Activity of C/EBPα.
TCERG1 was characterized previously as a repressor of the transcription factor C/EBPα through a mechanism that involved relocalization of TCERG1 from nuclear speckles to pericentromeric regions. The inhibitory activity as well as the relocalization activity has been demonstrated to lie in the amino terminal half of the protein, which contains several discrete motifs including an imperfect glutamine-alanine (QA) repeat. In the present study, we showed that deletion of this domain completely abrogated the ability of TCERG1 to inhibit the growth arrest activity of C/EBPα. Moreover, the QA repeat deletion mutant of TCERG1 lost the ability to be relocalized from nuclear speckles to pericentromeric regions, and caused an increase in the average size of individual speckles. We also showed that deletion of the QA repeat abrogated the complex formation between TCERG1 and C/EBPα. Examination of mutants with varying numbers of QA repeats indicated that a minimal number of repeats are required for inhibitory activity as well as relocalization ability. These data contribute to our overall understanding of how TCERG1 can have gene-specific effects in addition to its more general roles in coordinating transcription elongation and splicing.
Department of Biochemistry, University of Saskatchewan, Saskatoon, SK, Canada.
Nicholas J
NJ
Miller
Department of Biochemistry, University of Saskatchewan, Saskatoon, SK, Canada.
Kaitlyn
K
Schick
Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio.
Nikolai
N
Timchenko
Department of Biochemistry, University of Saskatchewan, Saskatoon, SK, Canada.
Emmett
E
Harrison
Department of Biochemistry, University of Saskatchewan, Saskatoon, SK, Canada.
William J
WJ
Roesler
D000818:Animals; D022762:CCAAT-Enhancer-Binding Proteins / Q000502:physiology*; D019556:COS Cells; D059447:Cell Cycle Checkpoints; D049109:Cell Proliferation; D002522:Chlorocebus aethiops; D057809:HEK293 Cells; D006801:Humans; D054730:Protein Interaction Domains and Motifs; D021381:Protein Transport; D035602:Transcriptional Elongation Factors / Q000737:chemistry* / Q000502:physiology
D022762:CCAAT-Enhancer-Binding Proteins; C515848:CEBPA protein, human; C108440:TCERG1 protein, human; D035602:Transcriptional Elongation Factors
CCAAT ENHANCER BINDING PROTEIN; CONFOCAL MICROSCOPY; GLUTAMINE-ALANINE REPEAT; NUCLEAR SPECKLES; SUBNUCLEAR COMPARTMENTALIZATION; TCERG1