Lecture 5 (myc)

Question 1

What is MYC?

Answer 1

Myc is a family of regulator genes and proto-oncogenes that encode for transcription factors

Question 2

MYC is overexpressed in what cancers:

Answer 2

Breast, Colon, Cervical, Lung, melanomas, glioblastomas, lymphoma

Question 3

How does post-translational modifications affect MYC.

Answer 3

It affects interaction with other proteins and transcriptional activity.

Question 4

What is Burkitt’s Lymphoma:

Answer 4

It is an aggressive B cell malignancy (cancer) associated with EBV infection.

Question 5

How is Burkitt’s Lymphoma caused:

Answer 5

Translocation of c-myc to Ig Heavy chain locus
(Which is a stronger promoter so MYC expression is increased)

Question 6

Structure of MYC

Answer 6

-Has a basic DNA binding domain followed by amino acid sequences forming an a-helix, a loop and a second a-helix.
-bHLH leucine zipper transcription factor.

Question 7

How can Myc become fully activated

Answer 7

By dimerizing with MAX at the leucine zipper region and phosphorylation at the transactivation domain (TAD)

Question 8

MYC/MAX binds to?

Answer 8

To the E-box sequence CACGTG of target genes to regulate gene transcription

Question 9

Binding of MYC/MAX to the EBOX leads to activation of what genes:

Answer 9

-E2F1, E2F2, E2F3
-Transcription factors, Cyclin D2 and CDK4
-CUL1

Question 10

EBOX stands for?

Answer 10

Enhancer Box

Question 11

How can MYC be targeted for degradation

Answer 11

Phosphorylation at Thr58 targets.
Therefore mutations at or near this residue are common in cancer.

Question 12

What is GSK3

Answer 12

GSK3 is a serine/threonine kinase, ubiquitously expressed and in resting cells is constitutively active, and inactivated by mitogenic signals.

Question 13

What is TRRAP

Answer 13

-TRRAP (transformation/transcription domain associated protein) is part of a complex that contains histone acetyl transferase (HAT) activity.
-TRRAP is involved in the MYC/MAX binding to EBOX.

Question 14

How can MYC be stabilized?

Answer 14

By phosphorylation at Ser62 by MAPK, a Ras downstream effector.

Question 15

MYC’s half life:

Answer 15

It is a short half life of 15-30mins.

Question 16

MYC levels are high when

Answer 16

There is an increase in mitogenic signals.

Question 17

Pathways that positively regulate MYC expression

Answer 17

Ras, Wnt, Notch, EGFR pathways

Question 18

Pathways that inhibit MYC expression

Answer 18

TGFb and BRCA1

Question 19

How MYC promotes cell cycle progression:

Answer 19

-Regulates cyclin D2 and CDK4 expression which are involved in the transition through G1 phase to S phase.
-Degrades CDKIs p27 and p21.
-Transcriptionally regulates CUL2.
-Phosphorylation of CDK2 by CAK allows active cyclin E/CDK2 to hyperphosphorylated RB which causes E2F to be released.
-Therefore, MYC promotes cell cycle progression by ultimately leading to expression of genes encoding E2F1, E2F2, E2F3 transcription factors which are used in S phase for DNA replication.

Question 20

How does MYC lead to reduced p15 and p21 expression

Answer 20

By binding to the transcription factor MIZ.

Question 21

MYC/MAX do what to p27

Answer 21

They positively regulate p27 degredation.

Question 22

What is the Warburg effect

Answer 22

When tumor cells use increased glucose uptake to grow.

Question 23

How does MYC activates Telomerase

Answer 23

By inducing expression of its catalytic subunit, telomerase reverse transcriptase (TERT).

Question 24

How does MYC positively regulates Angiogenesis

Answer 24

By upregulating VEGF expression

Question 25

MYC downregulates E-cadherin expression which leads to

Answer 25

To increased cell motility (invasiveness)