Pocket protein complexes are recruited to distinct targets in quiescent and proliferating cells

Egle Balciunaite1, Alexander Spektor, Nathan H Lents

  • 1Department of Pathology, MSB 504, New York University School of Medicine and New York University Cancer Institute, 550 First Avenue, New York, NY 10016, USA.

Insights

This study reveals distinct gene regulation by retinoblastoma protein (pRB) family members p107 and p130 in cycling cells. It identifies novel targets and regulatory networks specific to p107 and p130 in cell cycle progression.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Genetics

Background:

  • Retinoblastoma protein (pRB) tumor suppressor family members, including p107 and p130, have overlapping functions.
  • Distinguishing functional differences between p107 and p130 has been challenging.
  • Most studies focus on quiescent cells, overlooking distinct regulation in cycling cells.

Purpose of the Study:

  • To differentiate the functions of p107 and p130 in transcriptional regulation.
  • To investigate cell cycle-dependent gene regulation by pRB family members and E2F transcription factors.
  • To identify novel targets and regulatory networks of p107 and p130 in continuously cycling cells.

Main Methods:

  • Genome-wide chromatin immunoprecipitation (ChIP) to map protein-DNA interactions.
  • Analysis of histone acetylation signatures.
  • Mammalian Sin3B corepressor recruitment patterns.
  • Factor location analyses.

Main Results:

  • Distinct classes of genes are regulated by unique combinations of E2F4, p107, and p130.
  • A specific group of genes is regulated in cycling cells, differing from quiescent cells.
  • These gene groups show distinct histone acetylation and Sin3B recruitment patterns.
  • Novel and specific targets of p107 and p130 in cycling cells were identified.

Conclusions:

  • Cell cycle-dependent repression involves diverse recruited complexes, revealing differences between cycling and quiescent cell regulation.
  • p107 and p130 engage in distinct regulatory networks in continuously cycling cells.
  • This study provides new insights into the specific roles of p107 and p130 in cell cycle control.

Related Concept Videos

Protein Complexes with Interchangeable Parts01:57

Protein Complexes with Interchangeable Parts

Groups of proteins may form a complex where each protein in this complex has a different role in the overall execution of the complex’s function. Often some of the proteins in the complex can be replaced by a closely related variant to give a complex that contains many of the same components yet is functionally distinct.
The SCF ubiquitin ligase is a protein complex of five individual proteins. This complex attaches ubiquitin to other target proteins to mark them for degradation. In order to...
Protein Complex Assembly02:41

Protein Complex Assembly

Proteins can form homomeric complexes with another unit of the same protein or heteromeric complexes with different types.  Most protein complexes self-assemble spontaneously via ordered pathways, while some proteins need assembly factors that guide their proper assembly. Despite the crowded intracellular environment, proteins usually interact with their correct partners and form functional complexes.
Many viruses self-assemble into a fully functional unit using the infected host cell to...
Protein Complex Assembly02:41

Protein Complex Assembly

Proteins can form homomeric complexes with another unit of the same protein or heteromeric complexes with different types.  Most protein complexes self-assemble spontaneously via ordered pathways, while some proteins need assembly factors that guide their proper assembly. Despite the crowded intracellular environment, proteins usually interact with their correct partners and form functional complexes.
Many viruses self-assemble into a fully functional unit using the infected host cell to...
Nuclear Protein Sorting01:34

Nuclear Protein Sorting

Nuclear protein sorting is the selective trafficking of histones, polymerases, gene regulatory proteins into the nucleus and exporting RNAs and ribosomes to the cytosol. It is a tightly controlled process that regulates gene expression within a cell.
Proteins targeted to the nucleus carry nuclear localization signals or NLS recognized by import receptors in the cytosol. Similarly, proteins with nuclear export signals are recognized by export receptors. Import and export receptors are...
Assembly of Signaling Complexes01:30

Assembly of Signaling Complexes

Multiprotein signaling complexes are formed in a dynamic process involving protein-protein interactions at the cytoplasmic domain of transmembrane receptors or enzymatic and non-enzymatic proteins associated with the receptor. These complexes ensure the activation and propagation of intracellular signals that regulate cell functions.
Interaction domains in cell signaling
Interaction domains recognize exposed features of their binding partners containing post-translationally modified sequences,...
Negative Regulator Molecules01:23

Negative Regulator Molecules

Positive regulators allow a cell to advance through cell cycle checkpoints. Negative regulators have an equally important role as they terminate a cell’s progression through the cell cycle—or pause it—until the cell meets specific criteria.