p 57 & beckwith- wiedemann syndrome (bws)
DESCRIPTION
p 57 & Beckwith- Wiedemann syndrome (BWS). By: Adam Drechsler. CDK. CDK. Cyclin. Cyclin. CDK4. CDK4. Cyclin D. p16. p16. p57(kip2) is a CDK inhibitor. Ink4 Inhibitors. p57. Cip/Kip Proteins. p57. p57- location of action. p57 is : -A tumor suppressor - PowerPoint PPT PresentationTRANSCRIPT
By: Adam Drechsler
p57(kip2) is a CDK inhibitor
Cyclin
CDK p57
Cyclin
CDK p57
Cyclin D
CDK4 p16 CDK4
p16Ink4 Inhibitors
Cip/Kip Proteins
p57- location of action
p57 is:
-A tumor suppressor
-Localized to chromosome 11p15
-Down regulated by IGF-2
-An inhibitor of G1 Cyclin-CDK complexes
-At low levels a stimulator of cycD-CDK4/6
p57 Mouse Knockout
Targeted disruption of mouse p57(kip2) gene.
In the absence of p57…
p57 -/- : Embryonic/neonatal lethality, multiple developmental defects, altered cell proliferation and differentiation.
p57 +/- : Same as above, orWild-type expression
Genomic Imprinting Gene expressed in a parent-of-origin specific manner. Paternal imprint of p57
To add to the complexity… Highly variable penetrance
Displays subset of all phenotypes.
85% sporadic
CDKInhibitor Domain
ProlineRichDomain
AcidicDomain
QT Domain
Complex pattern of inheritance 15% of cases are familial
Autosomal dominant inheritance with variable expressivity (if mutated allele is inherited from mother)
Uniparental disomyTrisomy of chromosome 11p15.5Duplication of this chromosomeTranslocations involving maternal 11p.15.5
Beckwith-Wiedemann Syndrome
Growth abnormalities Somatic Overgrowth Macroglossia Gigantism Enlarged adrenal glands Ear creases Visceromegaly (enlarged organs) Omphalocele (umbilical hernia) Kidney abnormalities Advanced aging Birth weight and height > 90 percentile 1000-fold increase in risk of devloping childhood tumors.
Additional BWS information Good prognosis
Children usually grow up to become normal heights.
Mortality Risk Infant Mortality < 20%
Summary p57 is a cip/kip inhibitor p57 inhibits action by cyclin/cdk complexes
and prevents transition from G1 to S The paternal p57 gene is imprinted. p57 is high during embryogenesis and its
expression decreases toward adulthood 85% of cases are sporadic Loss of p57 function is the cause of
Beckwith-Wiedemann syndrome IGF-2 may play a role in the development
of BWS.