Tumor suppressor pRB functions as a co‐repressor of the CCAAT displacement protein (CDP/cut) to regulate cell cycle controlled histone H4 transcription

  title={Tumor suppressor pRB functions as a co‐repressor of the CCAAT displacement protein (CDP/cut) to regulate cell cycle controlled histone H4 transcription},
  author={Sunita Gupta and Mai X. Luong and Sylvia A Bleuming and Angela Miele and Michael Luong and Daniel W. Young and Erik S. Knudsen and Andre J. van Wijnen and Janet L. Stein and Gary S. Stein},
  journal={Journal of Cellular Physiology},
The CCAAT displacement protein (CDP‐cut/CUTL1/cux) performs a key proliferation‐related function as the DNA binding subunit of the cell cycle controlled HiNF‐D complex. HiNF‐D interacts with all five classes (H1, H2A, H2B, H3, and H4) of the cell‐cycle dependent histone genes, which are transcriptionally and coordinately activated at the G1/S phase transition independent of E2F. The tumor suppressor pRB/p105 is an intrinsic component of the HiNF‐D complex. However, the molecular interactions… 

HiNF‐P is a bifunctional regulator of cell cycle controlled histone H4 gene transcription

It is proposed that, analogous to E2F proteins and other cell cycle regulatory proteins, HiNF‐P is a bifunctional transcriptional regulator that can activate or repress cell cycle controlled genes depending on the cellular context.

The histone gene transcription factor HiNF-P stabilizes its cell cycle regulatory co-activator p220NPAT.

It is found that while Hi NF-P is maintained at steady-state levels throughout the cell cycle, both HiNF-P and p220NPAT are actively degraded by the proteasome pathway.

HiNF-P Directly Links the Cyclin E/CDK2/p220NPAT Pathway to Histone H4 Gene Regulation at the G1/S Phase Cell Cycle Transition

It is demonstrated that HiNF-P, a transcriptional regulator of replication-dependent histone H4 genes, interacts directly with p220NPAT, a substrate of cyclin E/CDK2, to coactivate histone genes during S phase.

Protein Kinase C-Mediated Modulation of FIH-1 Expression by the Homeodomain Protein CDP/Cut/Cux

It is demonstrated that in RCC, the Cut-like homeodomain protein (CDP/Cut) is involved in FIH transcriptional regulation and is controlled by a specific signaling event involving protein kinase C (PKC) ζ.

Crosstalk between E2F3 and p19ARF/p53 in the regulation of cell cycle progression and tumorigenesis

This work has established that the loss of E2f3 has multiple effects on cells that are relevant to tumor biology, and suggests that the regulation of cellular proliferation cannot be the only function of E 2F3 relevant to transformation and tumorigenesis.

Human replication-dependent histone H3 genes are activated by a tandemly arranged pair of two CCAAT boxes.

An initiation complex is formed on the histone H3 promoter that has a defined structure and limited flexibility, consisting of two molecules of CBF/NF-Y and further (general or specific) transcription factors.

SWI/SNF chromatin remodeling complex is obligatory for BMP2‐induced, Runx2‐dependent skeletal gene expression that controls osteoblast differentiation

Results support the concept that BMP2‐mediated osteogenesis requires Runx2, and demonstrates that initiation of B MP2‐induced, Runx 2‐dependent skeletal gene expression requires SWI/SNF chromatin remodeling complexes.



Cell cycle‐dependent modifications in activities of pRb‐related tumor suppressors and proliferation‐specific CDP/cut homeodomain factors in murine hematopoietic progenitor cells

Selective interactions of pRb and p107 with CDP/cut are observed during the FDC‐P1 cell cycle and suggest functional linkage to competency for DNA binding and/or transcriptional activity.

HiNF‐D (CDP‐cut/CDC2/cyclin A/pRB‐complex) influences the timing of IRF‐2‐dependent cell cycle activation of human histone H4 gene transcription at the G1/S phase transition

The main finding is that mutation of the HiNF‐D/CDP‐cut binding site alters the timing of histone gene activation during the cell cycle, and data indicate that hiNF‐P/H4TF‐2 may functionally compensate for Hi NF‐M/IRF‐2 at Site II to regulate histone H4 gene transcription in HeLa S3 cervical carcinoma cells during early S phase.

CDP/cut is the DNA-binding subunit of histone gene transcription factor HiNF-D: a mechanism for gene regulation at the G1/S phase cell cycle transition point independent of transcription factor E2F.

DNA replication-dependent histone H4 genes are regulated by an E2F-independent mechanism involving a complex of CDP/cut with cyclin A/CDC2/ RB-related proteins.

The integrated activities of IRF-2 (HiNF-M), CDP/cut (HiNF-D) and H4TF-2 (HiNF-P) regulate transcription of a cell cycle controlled human histone H4 gene: mechanistic differences between distinct H4 genes

It is postulate that the composite organization of Site II supports responsiveness to multiple signalling pathways modulating the activities of H4 gene transcription factors during the cell cycle.

Regulation of the homeodomain CCAAT displacement/cut protein function by histone acetyltransferases p300/CREB-binding protein (CBP)-associated factor and CBP.

The interaction of CDP/cut with CBP and p300/CREB-binding protein-associated factor (PCAF) along with the modification of C DP/cut by the histone acetyltransferase PCAF are reported, suggesting acetylation as a mechanism that regulates CDP /cut function.

Phosphorylation of the CCAAT Displacement Protein (CDP)/Cux Transcription Factor by Cyclin A-Cdk1 Modulates Its DNA Binding Activity in G2 *

The results suggest that the phosphorylation of CDP/Cux by cyclin A-Cdk1 contributes to down-modulate CDP /Cux activity as cells progress into the G2 phase of the cell cycle.

CDP and AP‐2 mediated repression mechanism of the replication‐dependent hamster histone H3.2 promoter

It is reported that the two CCAAT motifs within the H3.2 promoter confer transcriptional repression of the promoter during the cell cycle, and it is discovered that CDP can bind AP‐2, a ubiquitous factor that interacts with Rb.

Cell cycle controlled histone H1, H3, and H4 genes share unusual arrangements of recognition motifs for HiNF‐D supporting a coordinate promoter binding mechanism

The interactions of HiNF‐D with the H4, H3, and H1 promoters are modulated in parallel during the cessation of proliferation in both osteosarcoma cells and normal diploid osteoblasts, and these events occur in conjunction with concerted changes in histone gene expression.

Transcription of histone H4, H3, and H1 cell cycle genes: promoter factor HiNF-D contains CDC2, cyclin A, and an RB-related protein.

The presence of cell cycle mediators in the HiNF-D complex suggests linkage between transcriptional control of histones, enzymes involved in DNA synthesis, and the onset of DNA replication during the G1/S phase transition.

Identification of AP-2 as an interactive target of Rb and a regulator of the G1/S control element of the hamster histone H3.2 promoter.

It is demonstrated that over-expression of AP-2 proteins results in transactivation of the reporter gene through the H3core in a sequence-specific but orientation-independent manner, and may contribute to the cell cycle regulation of its target genes.