Lecture 1 - Nucleus

Question 1

Progeria

Answer 1

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)

Question 2

Nuclear lamins

Answer 2

A type of intermediate filament protein that is responsible for connecting chromatin to the inner nuclear membrane

Question 3

Laminopathies

Answer 3

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

Question 4

What state of phosphorylation are lamins in during interphase?

Answer 4

Dephosphorylated

Question 5

Is the nuclear membrane intact during interphase?

Answer 5

Yes

Question 6

When are lamins phosphorylated and what phosphorylates them?

Answer 6

In prophase by a kinase

Question 7

What is the result of lamin phosphorylation?

Answer 7

The chromatin-nuclear membrane connection breaks and the process of nuclear disassembly begins

Question 8

When are lamins returned to a dephosphorylated state and what does this?

Answer 8

Late in mitosis by a phosphatase

Question 9

What is the result of returning lamins to a dephosphorylated state?

Answer 9

Nuclear membrane assembly can occur

Question 10

Nuclear transport occurs via..

Answer 10

Nuclear pores

Question 11

What size molecules can enter the nucleus via diffusion through nuclear pores?

Answer 11

Cargo smaller than 5 to 10 kDa

Question 12

How are molecules that are larger than 5 to 10 kDa transported into the nucleus?

Answer 12

They are actively transported through nuclear pores

Question 13

What is required for cargo import?

Answer 13

Nuclear localization signals (NLS)

Question 14

What do chaperone proteins (e.g. importins) do?

Answer 14

They bind to NLS on cargo and escort it to nuclear pores

Question 15

Where is the wild type Huntington protein found and how big is it?

Answer 15

It is found in the cytoplasm and it is about 140 kDa

Question 16

Where is the defective Huntington protein found in patients with this disorder? What cell types are particularly affected?

Answer 16

They are found in the nucleus especially in brain neurons

Question 17

How does the Huntington protein make its way into the nucleus?

Answer 17

Evidence suggests that it is degraded in the cytoplasm into 5-10 kDa pieces that then passively diffuse into the nucleus through the pores

Question 18

True or false: The more Huntington protein in the brain neuron nuclei, the more severe and earlier onset the disease is.

Answer 18

True

Question 19

What are SINEs?

Answer 19

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

Question 20

True or False: Exportin-1 is down-regulated in cancer cells?

Answer 20

False

Question 21

What is the cargo of exportin-1?

Answer 21

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