Discovery of the Tumour Suppressor PTEN Flashcards
Timeline of PTEN discovery: 1984-97
Discovery that the loss of genetic material on chromosome 10 present in various cancer
Timeline of PTEN discovery: 1996-97
Transferring a normal chromosome 10 suppressed the tumourigenecity of certain brain tumours with mice suggesting the presence of a tumour suppressor protein on chromosome 10
Timeline of PTEN discovery: 1997
Two laboratories genetically mapped a tumour suppressor gene (PTEN) located on the frequently mutated chromosome 10 region q23.3
Timeline of PTEN discovery: 1997-98
PTEN was found to be mutated or deleted in a high percentage of brain, prostate, breast, and kidney cancer cell lines
Timeline of PTEN discovery: 2001-current
Subsequent studies concluded that mutations in the PTEN gene is a major event transforming tumours from a benign state to an aggressively malignant state
Who was bioinformatics originally coined by?
Hogeweg and Hesper
What was bioinformatics originally coined in 1970?
The study of informatic processes in biotic systems
What does bioinformatics combine?
A variety of disciplines to study biology in sillico
What are some of the principle applications of bioinformatics?
- Method development
- Computational tools
- Modelling
- Visualization
- Data storage
- Data curation
- Hypothesis generating
When is bioinformatics a powerful tool?
During functional characterization of a protein of interest
What types of fundamental bioinformatic tools are discussed?
- Prediction of protein function
- Database mining
How is the likely function of a protein of unknown function predicted?
By taking a primary protein sequence and basing it on a conserved domain search
What can database mining rapidly provide?
A database program where one can gather a wealth of organized information on any protein of interest
What was an AI breakthrough in biology?
Google DeepMinds
What was the predicted function of PTEN in the “Science” article from 1997?
- Has a protein tyrosine phosphatase domain and extensive homology to tensin, a protein that interacts with actin filaments at local adhesions
- These homologies suggest that PTEN may suppress tumour cell growth by antagonizing protein tyrosine kinase and may regulate tumour cell invasion and metastasis through interactions at focal adhesions
Why was PTEN predicted to be a protein phosphatase enzyme?
Multiple sequence alignments
When analyzing PTEN, what did conserved residues within orthologues suggest?
Divergence from classical PTPase superfamily for a specialized phosphatase function
What protein function databases are commonly used?
Ensembl and UniProt
What was a surprising function for PTEN noted in the “Science” article from 1998?
PTEN protein apparently exerts its effects by removing a phosphate from a lipid in one of the cell’s key growth control pathways
Where was the information on the physiological function of PTEN obtained?
Annotated database programs
What are lipids important for?
- Energy storage
- Membrane structure
- Mediating cell activation and signal transduction
What are Ptdlns?
Phosphoinositide polyphosphate lipids
What do Ptdlns serve as?
Anchoring platforms to recruit signaling proteins to specific cellular membrane compartments
How is the activity of Ptdlns determined?
By their phosphorylation state
Why are the enzymes that modify Ptdlns tightly regulated?
To properly execute signaling events
What disease states are common to the disruption of the balance of Ptdns?
- Cancer
- Diabetes
- Inflammation
- Cardiovascular disease
How does the PTEN tumour suppressor activity regulate cell growth?
When no PTEN is present there is too much PIP3 going to the proto-oncogene PKB/Akt leading to accelerated cell growth since some of PIP3 can’t also be used to regenerate back to PIP2 and Pi
