ROLE OF ANTIGEN P120 IN CELL PROLIFERATION

  • Freeman, James W (PI)

Project: Research project

Project Details

Description

Monoclonal antibodies have been developed and cDNAs isolated to a nucleolar
antigen (p120) that is detected in rapidly proliferating cells but not in
normal resting cells nor in many benign and slow growing malignant tumors.
In tumor cells, p120 is found in a novel DNA associated fibril-like
particle that is localized to a unique perinucleolar region. In cancer
cells the nucleolus in "hyperactive" and has a 15-100 fold greater rRNA
synthesis than in normal resting cells. The objectives of this study are
to determine whether p120 plays a role in this increased nucleolar
activity. The specific aims of this study are: to purify and characterize
p120 and its related nucleolar particle; to study the function of p120; and
to assess the regulation of p120 transcription and correlate p120
transcription levels to cell cycle potential. P120 will be purified from
its DNA associated nucleolar particle and amino acid composition, partial
amino acid sequence and DNA binding properties will be determined.
Inasmuch as p120 is proliferation related we will further characterize
proteins of the p120 particle and determine whether these peptides are
preferentially expressed in growing ells. The function of p120 will be
studied by assessing cell cycle progression, cytomorphological changes, and
rates of DNA and rRNA synthesis, following the microinjection of p120
antibodies or transfection of p120 antisense transcripts. Function will
also be evaluated following the addition of p120 antibodies or purified
protein to in vitro assays that measure nucleolar activation, rDNA
synthesis and rRNA transcription. P120 transcription levels and
transcription rates will be correlated with cell cycle progression and the
proliferative state of the cell. Studies will be done to determine whether
the regulation of p120 transcription differs between tumor cells and normal
proliferating cells. These studies will provide insight into the function
of p120; particularly the possible role of p120 in the maintenance of the
rapid proliferative state found in some cancer cells and in further
assessing the structural-functional relationship of the p120 related
nucleolar particle and its component parts with nucleolar activity and with
the proliferation state of the cell.
StatusFinished
Effective start/end date4/5/907/31/95

Funding

  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health: $89,073.00

ASJC

  • Medicine(all)

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