Lecture 5 + 6 Flashcards
Is c-myc is translocated in Burkitt’s Lymphoma
yes
How are MYC gene placed under highly active
transcriptional regulators
Translocation of c-myc to Ig Heavy chain locus
Is c-myc translocation sufficient for malignancy
No
How does MYC-MAX generate gene transcription
MYC-MAX heterodimer binds to E-box sequence CACGTG of target genes (or with noncanonical sequences) to regulate gene transcription
What targets MYC for degradation-mutations
Phosphorylation at Thr58
How is MYC stabilised
MYC is stabilised with phosphorylation at Ser62 by MAPK, a Ras downstream effector.
What do the TSGs p16 and ARF target
- target p53
Oncogenic stress-oncoprotein MYC-leads to E2Fs increase expression of ARF-activates p53 by binding to and sequestering its negative regulator MDM2. p53 levels
increase in the cell-leads to G1 and G2 arrest.
Is overexpression of MYC alone suffice to lead to cancer?
No, MYC alone cannot cause mitotic cellular division. Moreover, MYC overexpression can enforce replication in a manner that results in DNA breaks. This appears to be the consequence of several mechanisms. MYC may directly block double-stranded DNA repair and/or increase oxidative damage, causing DNA damage.
How does MYC activate Telomerase
by inducing expression of its catalytic subunit, telomerase reverse transcriptase
(TERT).
Does MYC binds MAX, to become transcriptionally active
Yes
How can MYC alter its transcriptional ability as well as its interaction with various interacting proteins
It is modified through various post-translational events including phosphorylation, acetylation and ubiquitination
What transcription factor is MYC
MYC is a bHLH leucine zipper transcription factor
What is involved in the positive regulation of MYC protein stabilization
MAPKs
MYC/MAX leads to the increased expression of target genes which have an E-Box of what genes
These include CDK4, CCND2 (gene for CyclinD2), CUL1.
MYC can become deregulated through chromosomal translocations as seen in Burkitt’s lymphoma
Yes