Molecular - White Flashcards
What makes cells different?
Differences in gene expression
What is the make up of a transcription factor?
N–DNA binding module — dimerization module — activation module —- regulatory module –C
Dimerization and regulatory are optional, DNA binding and activation are a must
Helix-turn-helix motif
Simplest; two alpha helices connect by a short chain of aas that make the “turn” at a fixed angle; longer helix portion = DNA binding module; helix-turn-helix proteins bind DNA as dimers
Zinc Finger domain
Includes Zn atom in the DNA binding motif; binds to major groove of DNA
Leucine supper motif
Two alpha helical DNA binding domains; dimerization through leucine zipper region; interactions b/w hydrophobic aa side chains (leucines) at every 7 aa down 1 side of alpha-helix –> forms zipper structure, grabs DNA like clothes pin
Helix loop helix domain
Consists of a short alpha chain connected by a loop to a second longer alpha chain. Can occur as homodimers or heterodimers. 3 domains: DNA binding domain, dimerization domain and activation domain.
What are the 2 ways in which RNA is de stabilzed?
- Decapping: exposed mRNA degraded from 5’ end (serves to protect RNA from RNA degrading enzymes)
- mRNA degraded from 3’ end through poly-A tail and into coding region
Post-translational processing and modifications
Required by proteins to be functional; proteins must fold into their 3D conformations helped by chaperones; bind cofactors
Ex: non-covalent interactions like folding and cofactor binding; covalent modification by glycosylation, phosphorylation, acetylation; binding to other subunits
Protea some
Apparatus that deliberately destroys aberrant protein
What are 2 examples of controls of gene expression?
- Methylation and genomic imprinting: what genes get expressed (or not) from mom and dad
- X-chromosome inactivation: even things out XX vs. XY - 2X chromosomes vs. 1 X chromosome
What are the 3 transition checkpoints in the cell cycle control system?
1: Start: G1 to S; cell commits to cell cycle entry and chromosome duplication
2. G2/M: move into chromosome alignment on spindle in metaphase
3. Metaphase to anaphase transition; trigger sister chromatid separation and cytokinesis
Cdks
Heart of cell-cycle control system; ACTIVITES of them rise and fall during cell cycle (not numbers); dependent on cyclins (must be bound to have protein kinase activity)
What are the proteins that regulate Cdks?
Cyclins
What is the property of Cdk when cyclin is not bound (inactive)?
The active site of Cdk is blocked by the T loop; binding cyclin causes the T loop to move out of the active site (Cdk partly active); phosphorylation of Cdk at T loop fully activates it (cave site)
What protein causes the phosphorylation of Cdk in the cave site to make it fully active?
CAK (Cdk activating kinase)
Condensin
At the end of S phase, chromosomes dramatically compact and sister chromatids become deistic separate units b/c of Condensin
What activates APC/C to complete mitosis?
M-Cdk
Force One in chromosome movement
Depolymerization: major force pulls the kinetochore and chromosome toward the spindle pole; depolymerization of the plus end of the microtubules drives the pulling of the kinetochore poleward
Force 2 of chromosome movement:
Microtubules flux: microtubules are moved toward spindle poles while being dismantled at minus ends; tubulin added at plus end while being removed at minus end
Force 3 of chromosome movement
Polar Ejection Force: kinesin 4, 10 motors on chromosomes interact w/ microtubules and transport chromosomes from poles; push pull phenomenon
Procaspases
Inactive caspase precursor
Executioner caspases:
Destroys actual target - executes apoptosis (caspase-3)
What forms the apoptosome?
When cytochrome c is released from mitochondria, it binds to a protein called Apaf1 to form it.
BH123 in apoptosis
BH123 proteins become activated, form aggregation in mitochondrial outer membrane and induce the release of cytochrome c - the apoptosome is formed
Bcl2 proteins
Blocks BH123 from aggregated and allowing release of cytochrome c
BH3-only protein
Inactivates Bcl2 to allow BH123 to aggregate
IAPs
Block caspases
Anti-IAPs
Neutralize the IAPs and liberate caspases
Oncogenes
Over activity mutation: GOF; involves single mutation event and activation of gene causing proliferation (dominant); “gas pedal”
Tumor suppressor genes
Under activity mutations; LOF; involve genes that inhibit growth. Mutation event: one gene - no effect; second mutation causes problems (recessive); “brakes”
What are the different ways proto-oncogenes can be activated in to oncogenes?
- Deletion or point mutation in coding sequence
- Regulatory mutation
- Gene amplification
- Chromosome rearrangement
What are the 2 major categories of tumor suppressor genes?
- Proteins that normally restrict cell growth and proliferation
- Proteins that maintain the integrity of the genome
Hereditary Rb
LOF or deletion of 1 copy of Rb in every cell b/c defect is inherited so predisposed to be cancerous; but have 1 good copy of Rb; somatic event occurs which elimates the good copy and get a loss of heterozygosity
Sporadic form of Rb
Cancerous cells have both copies of Rb mutated; 2 hit hypothesis; Rb is a regulator of the cell cycle
What mutation is important in colorectal cancer?
Loss in APC mutation - LOF; APC is a tumor suppressor gene
