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Developmental Genetics and Embryonal Cancers > c-myc > Flashcards

c-myc Flashcards

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Biology 101 flashcards
1
Q

What translocation occurs in Burkitts Lymphoma

A

t(8:14) –> puts the myc gene near the IgH gene promoter that is heavily expressed in B Cells

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2
Q

What 3 ways can activate c-myc in oncogenesis1

A

Proviral gene insertion
Amplification
Chromosomal Translocation

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3
Q

Describe the structure of the myc protein

A 
439a.a
2 Myc boxes
NLS
Basic Domain
LZ
HLH
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4
Q

What does c-myc bind to

A

E-box sequences

CACGTG

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5
Q

What is heterochromatin

A

DNA is densely packed

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6
Q

What is euchromatin

A

DNA is loosely packed

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7
Q

What are the 2 ways that RNA PolII Can Get access to chromsomes

A

Histone modification

ATP - dependent chromsome modification

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8
Q

Describe ATP-dependend chromosome remodelling

A

Complex protein binds to the nucelosome
ATP is used to move the nucleosome out of the way
Causes loosening of the chromsome
ALlows remodellign through octamer sliding or octamer transfer

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9
Q

What is open complex formation

A

When the template strand of DNA is seperated to allow access

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10
Q

What is the CTD

A

THe CTD is a 52 a.a. repeat motif that is bound to the RNA Pol II and its phosphorylation state helps describe the position of the polymerase

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11
Q

Describe the different phosphorylations that occur to RNA Pol II as it moves

A

Pre-Initiation - No Phosphorylation
Initiation: Ser5 Phosphorylation by TFIIH
Elongation: Phosphorylation at Ser2 by PTEFb
Termination: Removal of Ser5 phosphorylation by Ser5 phosphatase

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12
Q

What is Chip-Seq

A

Use formaldehyde to cross link bound protein to DNA
Isolate chromatin and shear the DNA
Precipirate chromatin with specific Ab
Reverse cross link and digest proteins
Construct a fradment library to allow it to undergo high density sequencing

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13
Q

What causes the proximal promoter pausing

A

NELF and DSIF

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14
Q

What releases promoter proximal pausing

A

PTEFb –> causes DSIF to be phosphorylated most important step as causes pause release
NELF Also disssociates from the complex but DSIF stays with it

THe whole process if important and is hence why myc is involved in transctiptional regulation

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15
Q

What dimerizes with myc

A

Max

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16
Q

What else can max bind with

A

Mad

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17
Q

Myc max causes whet

A

Transcriptional acitvation

18
Q

Mycmad causes what

A

Transcriptional repression

19
Q

How does myc max wor

A

Binds to E box
Recruits TRRAP –> recruits HATs.
Recruits PTEFb –> proximal pause release
Recruits SWI/SNF –> ATP dependent chromatin remodeller

20
Q

How does mycmad work

A

Recruits the SIN3 adaptor protein

This recruits HDACs

21
Q

How can myc max cause transcriptional repression

A

Prevents the interaction of Miz-1 and NPM1 by bidning to it hence prevents the transcriptional activity of Miz-1

22
Q

What is the rate limiting step of transcription

A

The recruitiment of pTEFb hence myc helps overcome this

23
Q

What do the other 2 RNA polymerases do

A

RNA Pol 1 - rRNA

RNA Pol II –> tRNA, 5srRNA, snRNA

24
Q

How does myc regulate RNA Pol I

A

Binds to E boxes

25
Q

How does myc regulate RNA Pol III

A

No E boxes hence interacts with TFIIIB and recruits HATs, specifically recruits GCNS, a specific HAT for RNA Pol III

26
Q

What genes does myc activate

A

Protein biosynthesis
Metablistm
Transcription factors and cell cycle e.e. E2F

27
Q

What genes does myc inhibit

A

CDKIs
Bcl-2
Cell Adhesion Molecules
Wnt Signalling Inhibitors

28
Q

How does myc induce apopotosis

A

Upregulates ARF ( as produces E2F)

29
Q

What form of myc causes differentiation

A

myc-nick

30
Q

How does myc-nick cause differentiation

A

Myc-nick lacks the DNA binding domain

Instead regulates alpha-tubulin acetylation throguh same acetyltransferases as in the nucelas, GCN5 specifically

31
Q

What are the four transcription factors involved in maintaining pluripotency in stem cells

A

C-myc
Oct4
Sox2
Klf4

32
Q

how is mRNA of myc regulated

A

Translational independent - involves the polyA tail shortening regualted by AU-rich regions in the 3’ UTR
Translational depenednt - regulated by the coding region determinant

33
Q

How does c-myc promote angiogenesis

A

Promotes the miR17-92 which downregulates thrombospandin - anigiogenesis

34
Q

Why is myc hard to target

A

Lacks hydrophobic pocket

Unorganized tertiary structure and protein-protein interactions

35
Q

How does EBV activate myc in Burkitts lymphoma

A

EBNA2 protein activates it

36
Q

What B Cell lymphomas is myc activated in

A

Burkitts
DLBLCL
Mantle cell lymphome
CLL –> poor prognosis if myc translocatoins. Richeter synrome (transformed CLL - 26% had myc alteratoins

37
Q

What T cell malignancies is myc activated in

A

Anaplastic large cell lymphoma
T-ALL
P-ALL

38
Q

What myeloid malignancies is myc deregulated in

A

AML and CML

39
Q

What gene fusion products can increase myc

A

RunXI-RUNXITI and PML-RARa

40
Q

How can we ratget myc deregulation

A

Target myc-max interaction
Increaese myc degradation
Target myc expression throguh epigenetic deregulation
How can we target myc associated vulnerabiltiesL Cell cycle inhibiton, resstablish apopotosis, protein biosynthesis

41
Q

What is the effect that we can exploit in cacner cells

A

The Wardburg effect which affects rapidly dividing cancer cells

42
Q

What post translational protein modifications can occur in myc

A

Proteasome inhbitiro (Bartezomib) can cause ER stress in cancers with myc i.e. multiple myeloma

Developmental Genetics and Embryonal Cancers (18 decks)

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