Arrest of the cell cycle by the tumour-suppressor BRCA1 requires the CDK-inhibitor p21WAF1/CiP1.

"this" "authored by" "Somasundaram K"
"this" "authored by" "Zhang H"
"this" "authored by" "Zeng YX"
"this" "authored by" "Houvras Y"
"this" "authored by" "Peng Y"
"this" "authored by" "Zhang H"
"this" "authored by" "Wu GS"
"this" "authored by" "Licht JD"
"this" "authored by" "Weber BL"
"this" "authored by" "El-Deiry WS"

"this" "authored at" "Laboratory of Molecular Oncology and Cell Cycle Regulation"
"this" "authored at" "Howard Hughes Medical Institute"
"this" "authored at" "Department of Medicine"
"this" "authored at" "University of Pennsylvania"
"this" "authored at" "School of Medicine"
"this" "authored at" "Philadelphia"
"this" "authored at" "19104"
"this" "authored at" "USA"

Much of the predisposition to hereditary breast and ovarian cancer has been attributed to inherited defects in the BRCA1 tumour-suppressor gene.

"hereditary breast cancer" "is a kind of" "breast cancer"
"mutated BRCA1 protein" "is a kind of" "BRCA1 protein"
"mutated BRCA1 gene" "is a kind of" "BRCA1 gene"
"BRCA1 mutated gene" "causes" "BRCA1 mutated protein"
"mutated BRCA1 protein" "causes" "hereditary breast cancer"
"mutated BRCA1 protein" "causes" "hereditary ovarian cancer"

The nuclear protein BRCA1 has the properties of a transcription factor, and can interact with the recombination and repair protein RAD51.

"BRCA1 protein" "is found in" "the cell nucleus"
"BRCA1 protein" "is a" "transcription factor"
"BRCA1 protein" "interacts with" "RAD51 protein"
"RAD51 protein" "is a" "recombination protein"
"RAD51 protein" "is a" "repair protein"

Young women with germline alterations in BRCA1 develop breast cancer at rates 100-fold higher than the general population, and BRCA1-null mice die before day 8 of development.

"mutated BRCA1 gene" "causes 100-fold higher rates of breast cancer in" "young women"
"missing BRCA1 protein" kills mice before day 8

However, the mechanisms of BRCA1-mediated growth regulation and tumour suppression remain unknown.

"BRCA1 protein" "regulates" "cell growth"

Here we show that BRCA1 transactivates expression of the cyclin-dependent kinase inhibitor p21WAF1/CIP1 in a p53-independent manner.

"BRCA1 protein" "causes expression of" "p21 protein"
"p21 protein" "inhibits" "cyclin-dependent kinases"
"p21 protein" "is also known as" "p21WAF1/CIP1"

BRCA1 inhibits cell-cycle progression into the S-phase following its transfection into human cancer cells.

"BRCA1 protein" "inhibits S-phase cell-cycle progression in" "human cancer cells"

BRCA1 does not inhibit S-phase progression in p21-/- cells, unlike p21+/+ cells

"BRCA1 protein" "does not inhibit S-phase cell-cycle progression in" "p21-/- cells"
"BRCA1 protein" "does inhibit S-phase cell-cycle progression in" "p21+/+ cells"

Tumour-associated, transactivation-deficient mutants of BRCA1 are defective in both transactivation of p21 and cell-cycle inhibition.

"S-phase" is a phase of "cell cycle"
"S-phase" is a synonym for "DNA Synthesis"
"cell cycle" "is a property of" "human cancer cells"
"BRCA1 mutant protein" "does not inhibit S-phase in" "human cancer cells"
"BCTumorCells" "are a kind of" "human cancer cell"

These data suggest that one mechanism by which BRCA1 contributes to cell-cycle arrest and growth suppression is through the induction of p21.

"BRCA1 protein" "induces" "p21 protein"
"p21 protein" "stops" "cell cycle"
"cell cycle" "is a property of" "normal cells"
"p21 protein" "stops" "cell growth"
"cell growth" "is a property of" "cell"

Add "MeSH Terms" to Standard Nomenclature
{
Animal
BRCA1 Protein/physiology*
BRCA1 Protein/genetics
Cell Cycle/physiology*
Cell Cycle/genetics
Cyclin-Dependent Kinases/metabolism
Cyclins/physiology*
Cyclins/genetics
COS Cells
DNA/biosynthesis
Enzyme Inhibitors/pharmacology
Gene Expression Regulation
Genes, Suppressor, Tumor
Hela Cells
Human
Luminescent Proteins
Mice
Mutation
Promoter Regions (Genetics)
Support, Non-U.S. Gov't
Support, U.S. Gov't, P.H.S.
Trans-Activation (Genetics)
Transfection
Tumor Cells, Cultured
}

Add "Substances" to Standard Nomenclature
{
DNA
green fluorescent protein
Luminescent Proteins
Enzyme Inhibitors
Cyclins
Cyclin-Dependent Kinases
Cip1 protein
BRCA1 Protein
}