Related Experiment Video

Updated: Jun 26, 2026

Detection of Aggregation-Prone Behavior in Mutant P53 V157F Breast Cancer Cells Using Multipoint Thioflavin T Fluorescence
04:56

Detection of Aggregation-Prone Behavior in Mutant P53 V157F Breast Cancer Cells Using Multipoint Thioflavin T Fluorescence

Published on: December 30, 2025

The tumor suppressor Cdc73 functionally associates with CPSF and CstF 3' mRNA processing factors

Orit Rozenblatt-Rosen1, Takashi Nagaike, Joshua M Francis

  • 1Department of Medical Oncology, Dana-Farber Cancer Institute, and Harvard Medical School, Boston, MA 02115, USA.

Proceedings of the National Academy of Sciences of the United States of America
|January 13, 2009
PubMed

Insights

The Cdc73 protein links tumor suppression to mRNA processing. It helps attach essential factors for 3' mRNA maturation, impacting gene regulation and potentially preventing parathyroid tumors.

Area of Science:

  • Molecular Biology
  • Cancer Genetics
  • RNA Processing

Background:

  • The CDC73 tumor suppressor gene is frequently inactivated in parathyroid tumors.
  • Cdc73 protein is a known component of the Paf1 complex, involved in RNA polymerase II regulation.

Purpose of the Study:

  • To investigate the role of Cdc73 protein in mRNA processing.
  • To identify direct targets and molecular mechanisms of Cdc73 function.

Main Methods:

  • Immunodepletion assays to assess the necessity of the Cdc73 complex in 3' mRNA processing.
  • Microarray analysis to identify Cdc73-regulated genes.
  • siRNA-mediated depletion of Cdc73 to study its in vivo effects on gene expression and chromatin association.

Main Results:

  • Cdc73 physically associates with cleavage and polyadenylation specificity factor (CPSF) and cleavage stimulation factor (CstF) complexes.
  • The Cdc73-CPSF-CstF complex is essential for 3' mRNA processing in vitro.
  • INTS6, encoding an Integrator complex subunit, was identified as a direct in vivo target of Cdc73.
  • Cdc73 depletion reduced INTS6 mRNA levels and the association of CPSF/CstF with the INTS6 gene locus.

Conclusions:

  • Cdc73 facilitates the recruitment of 3' mRNA processing factors to actively transcribed chromatin.
  • These findings highlight a crucial link between tumor suppression (via CDC73) and the fundamental process of mRNA maturation.

Related Concept Videos

Abnormal Proliferation02:23

Abnormal Proliferation

Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the daughter...
Separation of Sister Chromatids02:17

Separation of Sister Chromatids

At the transition from prophase to metaphase, there is a reduction in cohesion along the chromosomal arms, resulting in the resolution of sister chromatids. However, residual cohesin connections remain to hold the sister chromatids together until the transition from metaphase to anaphase. The residual connection prevents any premature separation of sister chromatids, blocking the risks of aneuploidy within the daughter cells.
At the onset of anaphase, separase, a proteolytic enzyme, is...
Anaphase Promoting Complex00:50

Anaphase Promoting Complex

The stepwise destruction of specific proteins is necessary for the progression and completion of the cell cycle. Such proteins are ubiquitinated by ubiquitin ligases and then subsequently destroyed by the proteasome. The SCF (Skp1/Cullin/F-box) and the anaphase-promoting complex (APC) are two important ubiquitin ligases involved in cell cycle progression. While SCF is active throughout the cell cycle, APC gets activated during metaphase to anaphase transition. Cdc20 or Cdh1 binds to APC and...
Cancer-Critical Genes II: Tumor Suppressor Genes01:05

Cancer-Critical Genes II: Tumor Suppressor Genes

Genes usually encode proteins necessary for the proper functioning of a healthy cell. Mutations can often cause changes to the gene expression pattern, thereby altering the phenotype.
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
Cancer-Critical Genes II: Tumor Suppressor Genes01:05

Cancer-Critical Genes II: Tumor Suppressor Genes

Genes usually encode proteins necessary for the proper functioning of a healthy cell. Mutations can often cause changes to the gene expression pattern, thereby altering the phenotype.
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
The Spindle Assembly Checkpoint02:19

The Spindle Assembly Checkpoint

The spindle assembly checkpoint is a molecular surveillance mechanism ensuring the fidelity of chromosome segregation during anaphase. The checkpoint monitors the completion of all the prerequisite steps before chromosome segregation to determine whether the segregation process should proceed or be delayed.
Many proteins function together to control the spindle assembly checkpoint. Mutations affecting these proteins may allow cells to proceed into anaphase prematurely, resulting in the...