Cell cycle gene expression networks discovered using systems biology: Significance in carcinogenesis.

The early stages of carcinogenesis are linked to defects in the cell cycle. A series of cell cycle checkpoints are involved in this process. The G1/S checkpoint that serves to integrate the control of cell proliferation and differentiation is linked to carcinogenesis and the mitotic spindle checkpoint is associated with the development of chromosomal instability.

SAFB1 interacts with and suppresses the transcriptional activity of p53.

A significant amount of nuclear p53 is found associated with the nuclear matrix in cells that were exposed to genotoxic stress. In this study we identified Scaffold attachment factor B1 (SAFB1), a nuclear matrix-associated protein that binds the scaffold or matrix attachment regions (S/MARs) of genomic DNA, as a novel p53-interacting protein. SAFB1 was able to associate with p53 through its C-terminal domain, while significant co-localization of the two proteins was observed in cells treated with 5-fluorouracil or mithramycin.

Systems genetics analyses predict a transcription role for P2P-R: molecular confirmation that P2P-R is a transcriptional co-repressor.

Background: The 250 kDa P2P-R protein (also known as PACT and Rbbp6) was cloned over a decade ago and was found to bind both the p53 and Rb1 tumor suppressor proteins. In addition, P2P-R has been associated with multiple biological functions, such as mitosis, mRNA processing, translation and ubiquitination. In the current studies, the online GeneNetwork system was employed to further probe P2P-R biological functions.

De-differentiation-derived mesenchymal stem cells demonstrate selective repression in H19 bioregulatory RNA gene expression.

Cellular de-differentiation can induce anticancer activity that makes cells resistant to carcinogenesis, but the molecular mechanism of this phenomenon has not been defined. To determine whether stable molecular changes develop in association with the process of de-differentiation, DNA microarray analyses were performed. These analyses compared control undifferentiated cells with three carcinogenesis-resistant clones of de-differentiated cells that were derived from mature adipocytes.

P2P-R expression is genetically coregulated with components of the translation machinery and with PUM2, a translational repressor that associates with the P2P-R mRNA.

P2P-R is a nuclear protein with potential functional roles in the control of gene expression and mitosis. The P2P-R protein also interacts with the p53 and Rb1 tumor suppressor proteins. To search for additional functional associations of P2P-R, we employed the WebQTL database that contains the results of cDNA microarray analysis on forebrain, cerebellum, and hematopoietic stem cell (HSC) specimens of multiple BXD recombinant inbred strains of mice.

Functional potential of P2P-R: a role in the cell cycle and cell differentiation related to its interactions with proteins that bind to matrix associated regions of DNA?

P2P-R is the alternately spliced product of the P2P-R/PACT gene in that P2P-R lacks one exon encoding 34 amino acids. The 250 kDa P2P-R protein is the predominate product expressed in multiple murine cell lines. It is a highly basic protein that contains multiple domains including an N-terminal RING type zinc finger, a proline rich domain, an RS region, and a C-terminal lysine-rich domain.

Traumatic hip dislocation in athletes.

Sports injuries are increasingly prevalent. Dislocations of the hip are rare; however, they are seen in high-velocity sports such as football and rugby. The injuries may be described as anterior or posterior, and classified according to severity of injury.

P2P-R protein overexpression restricts mitotic progression at prometaphase and promotes mitotic apoptosis.

Mitotic cells show a tenfold increase in immunoreactive P2P-R protein. During mitosis, the distribution of P2P-R protein also changes from a primary nucleolar localization in interphase cells to the periphery of chromosome in mitotic cells. These findings suggest that P2P-R might serve a functional role in mitosis.

P2P-R protein localizes to the nucleolus of interphase cells and the periphery of chromosomes in mitotic cells which show maximum P2P-R immunoreactivity.

P2P-R is a nuclear protein that can bind both p53 and Rb1. Its functions include roles in the control of RNA metabolism, apoptosis, and p53-dependent transcription. The expression of P2P-R also is repressed in G1 arrested terminally differentiated cells.