Functional communication between endogenous BRCA1 and its partner, BARD1, during Xenopus laevis development.
The breast and ovarian susceptibility protein 1 (BRCA1) heterodimerizes with its structural relative, the BRCA1-associated RING domain protein (BARD1), which may have tumor suppressing function in its own right. Both proteins have evolved from a common evolutionary ancestor, and both exist in Xenopus laevis where, similar to their mammalian homologs, they form functional heterodimers. Depleting frog embryos of either BARD1 or BRCA1 led to similar and widely defective developmental phenotypes as well as depletion of the other polypeptide due to its decreased stability. Thus, each protein, in part, controls the abundance, stability, and function of the other, and these effects are heterodimerization-dependent. The interdependent nature of BRCA1 and BARD1 function supports the view that BARD1/BRCA1 heterodimers play a major role in breast and ovarian cancer suppression.
Joukov
V
V
Dana-Farber Cancer Institute and Harvard Medical School, 44 Binney Street, Boston, MA 02115, USA.
Chen
J
J
Fox
E A
EA
Green
J B
JB
Livingston
D M
DM
D000818:Animals; D019313:BRCA1 Protein / Q000235:genetics / Q000502:physiology*; D001483:Base Sequence; D002352:Carrier Proteins / Q000235:genetics / Q000502:physiology*; D017124:Conserved Sequence; D018076:DNA, Complementary; D019281:Dimerization; D015870:Gene Expression; D006801:Humans; D008969:Molecular Sequence Data; D016376:Oligonucleotides, Antisense; D009865:Oocytes / Q000378:metabolism; D025521:Tumor Suppressor Proteins; D044767:Ubiquitin-Protein Ligases; D014982:Xenopus laevis / Q000196:embryology; D016335:Zinc Fingers / Q000235:genetics / Q000502:physiology*
D019313:BRCA1 Protein; D002352:Carrier Proteins; D018076:DNA, Complementary; D016376:Oligonucleotides, Antisense; D025521:Tumor Suppressor Proteins; C102449:BARD1 protein, human; D044767:Ubiquitin-Protein Ligases