High-risk HPV infection accounts for approximately what percent of
all cancers worldwide?

5%

E6: viral oncoprotein, inhibits what?

p53

E7: viral oncoprotein, inhibits what?

RB

BRC-Abl in chronic myelogenous leukemia (CML) is an example of what
type of alteration?

Generation of oncogenes by gene fusion through chromosome translocation

Two types of excessive expression of proto-oncogenes

chromosome translocation that juxtaposes strong
enhancer/promoter to proto-oncogene (Myc in Burkitt�s lymphoma).

gene amplification that increases the copy number of
a proto-oncogene (Myc in neuroblastoma, ErbB2 in breast cancer).

what is Trastuzumab (Herceptin)

a monoclonal antibody against Her2/Neu/ErbB2, a receptor tyrosine kinase

Gain-of-Function Mutations that Convert Normal Human Genes into Oncogenes

deletion or point mutation
regulatory mutation
gene amplification
chromosome rearrangement

The Knudsen Hypothesis of Retinoblastoma

Retinoblastoma results from TWO mutations in a single retinoblast.
Hereditary: Germline transmission of one mutation. Only one somatic
mutation (ONE HIT) in a retinoblast is required to cause cancer
Sporadic: De novo somatic mutations, Two mutations (TWO HITS)
occurring in one retinoblast.

properties of quiescent cells

metabolically less active than proliferating cells, do not express
genes required for DNA replication

mitogenesis

The process by which a quiescent cell becomes stimulated to prepare
for DNA replication and mitosis.

what are mitogens and what do they do?

ligands - can be growth factors cytokines and antigens and Wnts
(peptides), or hormones. They activate mitogenic signal transduction

endocrine signals

ligand circulates throughout the organism (systemic).

autocrine signals

ligand and the corresponding receptor expressed in the same cell (self-sufficient).

paracrine signals

ligand secreted or presented by neighboring cells (local).

what are Receptor Tyrosine Kinases and its properties?

They are Growth Factor Receptors with Tyrosine Kinase Activity.
N-terminal extracellular ligand binding domain. Single transmembrane
alpha helix. C-terminal intracellular protein tyrosine kinase
catalytic domain. region of homology is src.

Five general mechanisms/types of mutations that lead to deregulated
mitogenic signaling

1. gene amplification/overexpression
2. Loss of gene expression of homeostatic effector
3. Gene truncation that leads to a truncated protein
4. Gene fusion that leads a chimeric protein
5. Activating of inactivating point mutations in receptors or effectors

generalized function of SH2

1) phosphorylated 2) catalytically activated 3) allowed to interact
with other key signaling proteins

SH3 domain binds to what?

It binds to short Peptide sequence rich in Proline residues

SH2 domain binds to what?

It binds to short Peptide sequence with a phosphotyrosine (p-Tyr, pY)

what are the two binding regions of SH2 domain?

binding site for phosphotyrosine and for the amino acid side chain

what does the oncogenic mutation Q61L do?

inactivates GTPase of Ras

what does the oncogenic G12V mutation do?

it abolishes RAS-GTP binding to GAP

By Binding to Ras-GTP, the effectors are recruited to the plasma
membrane. order of effectors?

Ras-GTP - Raf - Mek - Erk1(all in cytoplasm) leads to promoter
activation in nucleus - induction of myc RNA - myc protein - reprogram
gene expression - cell proliferation

functions of BRAF mutations

activate BRAF kinase activity and MAPK signaling, can transform
NIH3T3 cells

Mechanisms of RTK inactivation:

dephosphorylation, endocytosis of receptor, often as result of
ubiquitylation, and by SHP1 a protein phosphatase that
dephosphorylates juxtamembrane tyrosines of kit.

Inhibitors of Cdk4/6

Ink4 family

inhibitors of CDK2 and CDC2

cip/kip familiy