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BIOM 3581A > Discovery of the Tumour Suppressor PTEN > Flashcards

Discovery of the Tumour Suppressor PTEN Flashcards

1
Q

Timeline of PTEN discovery: 1984-97

A

Discovery that the loss of genetic material on chromosome 10 present in various cancer

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2
Q

Timeline of PTEN discovery: 1996-97

A

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

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3
Q

Timeline of PTEN discovery: 1997

A

Two laboratories genetically mapped a tumour suppressor gene (PTEN) located on the frequently mutated chromosome 10 region q23.3

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4
Q

Timeline of PTEN discovery: 1997-98

A

PTEN was found to be mutated or deleted in a high percentage of brain, prostate, breast, and kidney cancer cell lines

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5
Q

Timeline of PTEN discovery: 2001-current

A

Subsequent studies concluded that mutations in the PTEN gene is a major event transforming tumours from a benign state to an aggressively malignant state

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6
Q

Who was bioinformatics originally coined by?

A

Hogeweg and Hesper

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7
Q

What was bioinformatics originally coined in 1970?

A

The study of informatic processes in biotic systems

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8
Q

What does bioinformatics combine?

A

A variety of disciplines to study biology in sillico

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9
Q

What are some of the principle applications of bioinformatics?

A
  • Method development
  • Computational tools
  • Modelling
  • Visualization
  • Data storage
  • Data curation
  • Hypothesis generating
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10
Q

When is bioinformatics a powerful tool?

A

During functional characterization of a protein of interest

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11
Q

What types of fundamental bioinformatic tools are discussed?

A
  • Prediction of protein function
  • Database mining
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12
Q

How is the likely function of a protein of unknown function predicted?

A

By taking a primary protein sequence and basing it on a conserved domain search

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13
Q

What can database mining rapidly provide?

A

A database program where one can gather a wealth of organized information on any protein of interest

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14
Q

What was an AI breakthrough in biology?

A

Google DeepMinds

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15
Q

What was the predicted function of PTEN in the “Science” article from 1997?

A
  • 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
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16
Q

Why was PTEN predicted to be a protein phosphatase enzyme?

A

Multiple sequence alignments

17
Q

When analyzing PTEN, what did conserved residues within orthologues suggest?

A

Divergence from classical PTPase superfamily for a specialized phosphatase function

18
Q

What protein function databases are commonly used?

A

Ensembl and UniProt

19
Q

What was a surprising function for PTEN noted in the “Science” article from 1998?

A

PTEN protein apparently exerts its effects by removing a phosphate from a lipid in one of the cell’s key growth control pathways

20
Q

Where was the information on the physiological function of PTEN obtained?

A

Annotated database programs

21
Q

What are lipids important for?

A
  • Energy storage
  • Membrane structure
  • Mediating cell activation and signal transduction
22
Q

What are Ptdlns?

A

Phosphoinositide polyphosphate lipids

23
Q

What do Ptdlns serve as?

A

Anchoring platforms to recruit signaling proteins to specific cellular membrane compartments

24
Q

How is the activity of Ptdlns determined?

A

By their phosphorylation state

25
Q

Why are the enzymes that modify Ptdlns tightly regulated?

A

To properly execute signaling events

26
Q

What disease states are common to the disruption of the balance of Ptdns?

A
  • Cancer
  • Diabetes
  • Inflammation
  • Cardiovascular disease
27
Q

How does the PTEN tumour suppressor activity regulate cell growth?

A

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

BIOM 3581A (17 decks)

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