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Printable Handouts
Navigable Slide Index
- Introduction
- Outline
- Regulation of cell growth
- Cell size changes in normal physiology
- Disease-associated changes in cell size
- Dual growth signals in multicellular organisms
- Rapamycin and its uses
- Rapamycin decreases cell size
- Effect of pre-natal exposure to rapamycin
- Effect of post-natal exposure to rapamycin
- Rapamycin acts via a gain-of-function mechanism
- The mTOR pathway regulates growth (2002)
- What are the components of the mTOR pathway?
- mTOR likely interacts with other proteins
- mTOR associated proteins
- Identification of raptor and Gable
- The mTOR Complex 1 (mTORC1) pathway
- Loss of raptor reduces mTORC1 signaling in mice
- Loss of raptor reduces liver and hepatocyte size
- How is the mTORC1 pathway regulated?
- The problem: no in vitro regulation of mTORC1
- Regulation of mTORC1 by insulin
- mTORC1 is downstream of cancer pathways
- mTOR exists in two distinct protein complexes
- The odd behavior of a mutant of S6K1
- Common structural features in AGC kinases
- Unknown Ser473 kinase important in Akt activation
- mTORC2 regulates Akt in vitro and in cells
- Biochemical analysis of embryos lacking rictor
- mTORC2 is part of the PI3K/PTEN pathway
- Akt signaling is important in many key processes
- Role of mTORC2 in prostate tumorigenesis
- Normal murine prostate
- Histological phenotype of PTEN null prostates
- Loss of PTEN and mTORC2 (1)
- Loss of PTEN and mTORC2 (2)
- mTORC2 inhibition normalizes hyper-proliferation
- The mTOR pathway (2002)
- Connections of mTOR to cancer
- The mTORC1 and mTORC2 pathways
- The Rag-Ragulator important for mTORC1 function
- Laboratory members (1)
- Laboratory members (2)
Topics Covered
- Introduction to growth control
- Cell size changes in normal physiology
- Dual growth signals in multicellular organisms
- Rapamycin and its uses
- Discovery and function of mTOR growth pathways
- raptor and GL
- The mTOR Complex 1 (mTORC1) pathway
- mTOR exists in two distinct protein complexes: mTORC1 and mTORC2
- The role of the mTOR pathway in cancer
Links
Series:
Categories:
Therapeutic Areas:
Talk Citation
Sabatini, D. (2010, December 14). The mTOR kinase as a target for anti-cancer drugs [Video file]. In The Biomedical & Life Sciences Collection, Henry Stewart Talks. Retrieved December 5, 2024, from https://doi.org/10.69645/CHQN3336.Export Citation (RIS)
Publication History
Financial Disclosures
- Prof. David Sabatini has not informed HSTalks of any commercial/financial relationship that it is appropriate to disclose.
A selection of talks on Biochemistry
Transcript
Please wait while the transcript is being prepared...
0:00
Hello, my name is David Sabatini.
I'm at the Whitehead Institute and the
MIT Department of Biology as well as part of the Howard Hughes Medical Institute.
I'm going to be talking to you today about the mTOR Kinase and
particularly its role as a potential target for anti-cancer drugs.
0:18
I'm going first give you a little bit of introduction into
the role of mTOR in the regulation of growth because it's
normal physiological role which becomes aberrant in human pathologies such as in cancer.
I'll tell you a little bit as well about the discovery and
the function of the mTOR growth pathways.
As you'll see, there's actually two pathways.
So, I think this has been a very interesting area
of signal transduction over the last decade.
0:43
So, what do we mean by the control of growth?
This is really the regulation of size in biology and we can think
about the control of size in biology at multiple different biological levels.
For example, the regulation of cell size,
the regulation of organ size, or organismal size.
The TOR pathway, the mTOR pathway as we call it,
in mammalian systems, really regulates size at all these different biological levels.
But today, I'll focus about its role in the control of growth at the level of cell size.
So, what do we mean by cell growth then?
Well, this is the process by which a cell takes nutrients from its environment,
generates the building blocks for cell mass,
as well as the energy sources,
and increases in size.
Clearly, for proliferating cells,
such as cancer cells,
growth must occur before cell division.
Otherwise, the cell would divide itself into oblivion.
In fact, there are ways that you can trick cells into doing this.
However, even though we know that growth and cell division must be coordinated,
we actually know relatively little about what coordinates these two processes,
particularly, in mammalian systems.
If we think about the regulation of cell size in normal physiology in mammals,