Lecture 1 - Nucleus Flashcards
Progeria
A rare genetic disease in which patients age so rapidly, they die in their second decade of life from advanced atherosclerosis (typically a disease of the elderly)
Nuclear lamins
A type of intermediate filament protein that is responsible for connecting chromatin to the inner nuclear membrane
Laminopathies
A new class of diseases due to defective lamins such as progeria, lipodystrophy, cardiomyopathy (rare forms), muscular dystrophy (rare forms), mandibular acryldysplasia, atypical werner’s syndrome, and restrictive dermopathy
What state of phosphorylation are lamins in during interphase?
Dephosphorylated
Is the nuclear membrane intact during interphase?
Yes
When are lamins phosphorylated and what phosphorylates them?
In prophase by a kinase
What is the result of lamin phosphorylation?
The chromatin-nuclear membrane connection breaks and the process of nuclear disassembly begins
When are lamins returned to a dephosphorylated state and what does this?
Late in mitosis by a phosphatase
What is the result of returning lamins to a dephosphorylated state?
Nuclear membrane assembly can occur
Nuclear transport occurs via..
Nuclear pores
What size molecules can enter the nucleus via diffusion through nuclear pores?
Cargo smaller than 5 to 10 kDa
How are molecules that are larger than 5 to 10 kDa transported into the nucleus?
They are actively transported through nuclear pores
What is required for cargo import?
Nuclear localization signals (NLS)
What do chaperone proteins (e.g. importins) do?
They bind to NLS on cargo and escort it to nuclear pores
Where is the wild type Huntington protein found and how big is it?
It is found in the cytoplasm and it is about 140 kDa
Where is the defective Huntington protein found in patients with this disorder? What cell types are particularly affected?
They are found in the nucleus especially in brain neurons
How does the Huntington protein make its way into the nucleus?
Evidence suggests that it is degraded in the cytoplasm into 5-10 kDa pieces that then passively diffuse into the nucleus through the pores
True or false: The more Huntington protein in the brain neuron nuclei, the more severe and earlier onset the disease is.
True
What are SINEs?
Selective Inhibitors of Nuclear Export are small molecules that bind to, and block, the pocket on exportin-1 and prevent it from exporting tumor suppressors from the nucleus where they work
True or False: Exportin-1 is down-regulated in cancer cells?
False
What is the cargo of exportin-1?
Tumor suppressors, apoptosis inducers, and anti-proliferative molecules or cell cycle inhibitors that exert their normal biological activities via binding to DNA in the nucleus
