OCT 11, 2018 9:00 AM PDT

Destabilization and Degradation of MYC: More Ways Than One

Speaker
  • Post-Doctoral Fellow, Princess Margaret Cancer Research, University Health Network
    Biography
      Dr. Jason De Melo is a post-doctoral fellow in the laboratory of Dr. Linda Penn at the Princess Margaret Cancer Centre in Toronto, Canada where his work focuses on elucidating a new degradation pathway for the MYC oncoprotein. Prior to his current position, Jason graduated from the University of Waterloo with a B.Sc in Biochemistry with a specialization in Biotechnology. His studies included work placements at Environment Canada, the Public Health Agency of Canada and Lorus Therapeutics. Jason then moved to McMaster University where he studied under the supervision of Dr. Damu Tang, graduating with a Ph.D. in Medical Sciences. Jason's work examined the role of SHARPIN in the regulation of the tumoursuppressor PTEN in Breast Cancer. In addition to his research work, Jason now teaches a course on Genome Editing at the Michener Institute for Education at UHN.

    Abstract

    The oncogenic transcription factor c-MYC (MYC) is deregulated, and often overexpressed, in more than 50% of cancers. MYC deregulation is associated with poor prognosis and aggressive disease, suggesting that the development of therapeutic inhibitors targeting MYC would dramatically impact patient care and outcome. MYC is a highly regulated transcription factor, with a protein and mRNA half-life of approximately 30 min. The most extensively studied pathway regulating MYC protein stability involves ubiquitylation and proteasomal degradation mediated by the E3-ligase, SCFFbxw7. We provide evidence for a SCFFBXW7-independent regulatory mechanism centered on Lysine 52 (K52) within MYC Box I (MBI) of the MYC protein. This residue has been shown to be post-translationally modified by both ubiquitylation and SUMOylation, hinting at the interplay of post-translational modifications at this site, and the importance of this residue. We demonstrate that mutation of K52 to arginine (R) renders the MYC protein more labile. Mechanistically, we show that the degradation pathway regulated by K52 is independent of the Cullin-Ring-Ligase (CRL) family of E3-ligases, which includes not only the canonical SCFFBXW7, but also a number of other known MYC-targeting E3-ligases, such as SCFSKP2, SCFβTCRP, SCFFBXO28 and DCXTRUSS. To characterize this degradation pathway further we will utilize unbiased and targeted experiments to elucidate the proteins involved. Taken together, our data identifies a novel regulatory pathway centred on K52 that may be exploited for the development of anti-MYC therapeutics. 

    Learning Objectives: 

    1. Learn about the critical role of MYC in tumorigenesis
    2. Understand the relationship between the amount of MYC protein in the cell and its tumorigenicity
    3. Understand how the stability of the MYC protein is regulated in the cell


    Show Resources
    You May Also Like
    MAY 11, 2021 10:00 AM PDT
    Add to Calendar Select one of the following: iCal Google Calendar Outlook Calendar Yahoo Calendar
    C.E. CREDITS
    MAY 11, 2021 10:00 AM PDT
    Add to Calendar Select one of the following: iCal Google Calendar Outlook Calendar Yahoo Calendar
    Date: May 11, 2021 Time: 10:00zm PDT Your samples are some of the most valuable assets in the laboratory. After spending countless hours on extraction and preparation, your conclusions could...
    JUN 09, 2021 7:00 AM PDT
    Add to Calendar Select one of the following: iCal Google Calendar Outlook Calendar Yahoo Calendar
    C.E. CREDITS
    JUN 09, 2021 7:00 AM PDT
    Add to Calendar Select one of the following: iCal Google Calendar Outlook Calendar Yahoo Calendar
    Date: June 9, 2021 Time: 09 June 2021, 7am PDT, 10am EDT, 4pm CEST cells with dramatic implications on the validity of past cell culture related research. The fact that at least 509 cell lin...
    DEC 02, 2020 8:00 AM PST
    C.E. CREDITS
    DEC 02, 2020 8:00 AM PST
    DATE: December 2nd, 2020 TIME: 08:00am PDT, 11:00pm EDT Bioreactors and shakers are used to cultivate microorganisms, plant, insect, and mammalian cells in different volumes. Upscaling of pr...
    NOV 16, 2020 8:00 AM PST
    C.E. CREDITS
    NOV 16, 2020 8:00 AM PST
    Date: November 16, 2020 Time: 8:00am (PST), 11:00am (EST) CRISPR screening has become the prime discovery tool in modern biomedical research and drug discovery. At the same time, most screen...
    NOV 18, 2020 8:00 AM PST
    C.E. CREDITS
    NOV 18, 2020 8:00 AM PST
    DATE: November 18, 2020 TIME: 08:00am PDT We develop and implement technologies to solve some of the major bottlenecks in biomedical research. In particular, we establish new imaging approac...
    OCT 29, 2020 6:00 AM PDT
    C.E. CREDITS
    OCT 29, 2020 6:00 AM PDT
    Date: October 29, 2020 Time: 6:00am (PDT), 9:00am (EDT), Chronic inflammation can occur as a result of a combination of genetic predispositions and environmental factors. Epigenetic modifica...
    OCT 11, 2018 9:00 AM PDT

    Destabilization and Degradation of MYC: More Ways Than One


    Specialty

    Research

    Bioinformatics

    Lab Safety

    Pcr/rt-Pcr/real-Time Pcr

    Infectious Disease

    Gene Expression

    Health

    Cancer Diagnostics

    Research And Development

    Cytogenetics

    Molecular Biology

    Genetics

    Earth Science

    Cancer Research

    University

    Geography

    North America50%

    Asia50%

    Registration Source

    Website Visitors100%

    Job Title

    Medical Laboratory Technician100%

    Organization

    Manufacturer - Other50%

    Other50%


    Show Resources
    Loading Comments...
    Show Resources
    Attendees
    • See more