Spotlight on Talent
DR. FRED DICK
Retinoblastoma Protein: Chief Traffic Controller of the Cell Cycle
Traffic control is crucial to our communities: traffic lights and road signs co-ordinate traffic flow and impose safety and order on our streets. We’ve all encountered that drive to work on a rainy morning when a stop light malfunctions at a bustling intersection. How quickly order crumbles to create a major traffic jam! Tempers flare and swear words abound! Drivers must decide when to stop and start, resulting in disorganized crossing of the intersection. In such situations, we are keenly aware of the importance of traffic control for our busy roads. Traffic controllers also exist in cells in the form of key proteins that regulate cellular functions. Retinoblastoma protein (Rb) is one such regulator that plays an integral role in controlling cell cycle traffic.
Rb affects several cellular processes, in addition to the cell cycle. Rb inhibits apoptosis, regulates cell differentiation during development, and maintains chromosomal stability. In the cell cycle, Rb serves as the traffic controller at the G1 checkpoint. Here, Rb influences whether cells can proceed from the G1 (Gap 1) to S (synthesis) phase, a necessary step for cell cycle progression. Rb blocks the cell cycle through several mechanisms that inhibit cellular traffic involved in G1 to S phase entry. One such mechanism involves Rb interaction with E2F transcription factors, thus preventing expression of protein traffic involved in cell cycle entry. Rb’s role as a traffic controller is critical for imposing order on cell growth and division. Loss of Rb function is akin to the traffic jams that result when traffic control is lost in the human world: disordered cellular traffic, uncontrolled growth, and often, cancer result. The fact that Rb is inactivated or mutated in most human cancers highlights Rb’s importance as a tumour suppressor.
Rb interacts with >100 binding partners, functioning as a transcription co-factor and as an adaptor protein. In the first role, Rb interacts with transcription factors to activate or inhibit them, resulting in subsequent changes in gene expression. In its second role as an adaptor protein, Rb binds to specific partners to regulate downstream effects, usually influencing gene expression. Although many Rb partners are known, much remains to be discovered about the co-ordination of their downstream functions and the contributions of these effects to cancer suppression.
Dr. Fred Dick in the Dept. of Biochemistry at the University of Western Ontario studies Rb structure-function relationships in order to understand this protein’s role in cell cycle control and cancer. He examines key structural features of Rb that mediate partner interactions and how such binding contributes to Rb’s inhibition of the cell cycle and tumour progression. Dr. Dick’s research involving Rb encompasses two projects. In his first area of research, Dr. Dick explores the function of two Rb structural interfaces that allow interaction with E2F1. Dr. Dick is examining how Rb-E2F1 binding is controlled at these two sites and the resulting downstream effects on apoptosis and cell cycle progression. In Dr. Dick’s second area of research, he studies the function of Rb’s LXCXE binding cleft. This pocket interacts with the LXCXE amino acid motif (Leu X Cys X Glu; X= intervening amino acids) found in certain Rb binding partners. He examines the role of such interactions in Rb’s regulation of chromatin structure and the cell cycle. He also identifies new partners that interact with Rb’s LXCXE cleft.
To study Rb’s role as the traffic controller of the cell cycle, Dr. Dick uses a combination of molecular biology, biochemical assays, cell culture, and transgenic mice. He produces recombinant Rb forms that have mutations in partner binding sites. The mutated proteins are then tested for their ability to bind partners and elicit downstream effects, such as apoptosis, chromatin changes, and cell cycle arrest. Any promising Rb mutations are incorporated into transgenic mice for examination of cancer susceptibility.
Dr. Dick’s research sheds light on how Rb functions to regulate cell cycle traffic. Such work holds promise for the development of therapeutics to combat cancer in which Rb control over cell cycle progression is lost. Unsnarling cell cycle traffic jams is the way of the future for Dr. Dick.
This research is funded by the Canadian Institutes of Health Research (CIHR), Canadian Cancer Society Research Institute, Cancer Research Society, Ministry of Research and Innovation (MRI), and the University of Western Ontario.
© Lynn Weir, 2009
Profile for Dr. Fred Dick
Contact Information
Dr. Fred Dick
Associate Professor - Department of Biochemistry, University of Western Ontario
Cancer Research Laboratories
Room A4136, Victoria Research Laboratory
790 Commissioners Rd. East
London, ON N6A 4L6
519-685-8620
fdick@uwo.ca
Webpage for Fred Dick
Publications
Education
- BSc (University of Western Ontario, London, ON, Canada)
- PhD (Dartmouth Medical School, Hanover, NH, USA)
- Post-doctoral researcher (Massachusetts General Hospital Cancer Center, Boston, MA, USA)
Research Expertise
- retinoblastoma protein (pRB)
- tumour suppressors
- transcription factors
- chromatin structure
- epigenetics
- cell division
Research Applications
- cancer (breast)
Favourite Molecule
- The retinoblastoma protein
Favourite Website
Interests
- I enjoy playing soccer with the members of my lab.
Updated by Lynn Weir, Aug 2009
