cell cycle and cancer development Flashcards
hormones
molecule produced and secreted by one cell type (gland), transported to second target cell to elicit biological response
growth factors
signaling proteins that act as mitogens to stimulate cell growth and proliferation of a target cell; also active at very low concentrations
receptors
target cell proteins that bind growth factors and hormones with very high affinity and specificity
signal transduction
process that converts the binding of a signaling molecule to its target cell receptor to elicit a biological response
second messengers
agents of signal transduction within the target cell
cancer is a disease resulting from…
an accumulation of mutations and epigenetic modifications in genes that regulate cell growth and division; favor increase in the rate of cell growth; cancer cells are invasive
all cancers are ________, but not all are ___________
invasive; metastatic
cancer is not an equal opportunity disease. what does this mean?
some organs/tissues are more prone to develop cancer than others. most somatic cells do not undergo cell division
organs that require regular replenishment are ___________________
- cells in the skin, blood, and digestive tract undergo constant turnover
- cell types that do not undergo replenishment such as muscle and neurons do no develop into cancer cells
at greater risk
cancer is most likely to develop in _______________
the epithelium of organs
cancer is a genomic disease. what does this mean?
cancer is associated with aging. mutations accumulate over a lifetime. the longer you live, the more likely you are to develop cancer
proto-oncogenes
normal gene that encodes a protein promoting cell growth and proliferation
oncogene
mutant form that favors excessive growth and contributed to cancer development
- a gain of function in one allele is sufficient for accelerated growth
tumor suppressor gene
encodes a protein that normally inhibits cell growth and proliferation
- loss of function mutations favors excessive growth and contributes to cancer development
- (most instances) loss of both alleles is required for complete loss of function
_____________ and _________________ signaling are used for production fo cell cycle proteins needed for progression through the cell cycle
growth factor and hormone-induced
mechanisms of cell signaling
endocrine- long range
paracrine- close range
autocrine- same cell has receptors and signals
juxtacrine- right next to each other
protein signaling molecules require a ______________. hydrophobic signaling molecules, such as steroid hormones, use ________________
cell membrane receptor; nuclear receptors
__________________ exists in the cytoplasm
- estrogen binding induces dimerization of ER
- ER binds to genes containing an ________________________ sequence
- ER interacts with _____________ proteins for the recruitment of transcription machinery
estrogen receptor; estrogen response element (ERE); coactivator
One of the genes that contains an ERE sequence is the _____ gene. _____ is one subunit of _____
JUN; JUN; AP-1
__________ is an estrogen antagonist
Tamoxifen
peptides affect target cells via plasma membrane-associated receptors. Some of these are GCPRs, others are _______________________
these receptors are transmembrane proteins that contain both intracellular and extracellular domains
RTKS (receptor tyrosine kinases)
_____________ binds to RTK phosphorylated sites
- _____ is a _____________________
- ____ activity results in GDP/GTP exchange by _____
SOS1 complex; SOS1; guanine nucleotide exhange factor (GEF); SOS1; RAS
active RAS activates _________________. RAS signaling is turned off by ____________________________
signaling cascade; GTPase activating protein (GAP)
sequential activation of protein kinases results in _____________ and _________________, an example of a ____________________.
signal amplification; diversification; signaling cascade
this pathway is activated by RTKs for many growth factors, such as IGF-1, EGF, and PDGF
- _______ interacts with ____, activating its protein kinase activity
- _____ phosphorylates _____
- _____ phosphorylates ____
- ____ phosphorylates transcription factors in the nucleus
RAS-GTP; RAF; RAF; MEK; MEK; ERK; ERK
______ binds Serum Response Element (SRE) located in genes to activate transcription. ____ is one of these genes
ELK-1; FOS
phosphorylation and activity of target proteins reversed by _____________
protein phosphatases
what defines each phase in the cell cycle?
cyclin D
_______ is a _______________ that can activate the RAS-dependent pathway
HER2; receptor tyrosine kinase
_______________ is an increase in gene copy number as the result of a localized error in replication along a chromosome
amplification
______________ is a synthetic antibody that binds to Her2 monomers
herceptin
___ family are prominent proto-oncogenes
RAS
what is the most common mutation of RAS in lung cancers?
G12C
(G= normal gene, 12= position C= new mutant gene)
JUN and FOS proteins form the transcription factor ____________. ____ is an essential activator for many genes needed for progression through the cell cycle.
activation protein 1; AP-1
____ and _____ are _______________
JUN and FOS; early response genes
AP-1 is __________________
- FOS has no activity by itself
- JUN/JUN homodimer AP-1 is a much weaker transcription factor than JUN/FOS
- binds to the TRE cis-acting regulatory sequence in genes that regulate cell proliferation
leucine zipper transcription factor
the _________ is driven by synthesis and degradation of the _________________
cell cycle; cyclin proteins
a _______ complexes with a ___________________ in a 1:1 stoichiometry
cyclin; cyclin-dependent kinase (cdk)
upregulation of ________ gene transcription by _____ and _____ kick starts the cell cycle
cyclin D; AP-1 and MYC
the cell cycle has a ______________, and if the cell passes this point, it is committed to replication
restriction point
___________________ present a ‘wall’ of inhibition in GI. cdk activity must overcome this inhibition.
cdk inhibitors or CKIs
__________________ proteins bind to _______ in 1:1 stoichiometry blocking ________ binding
inhibitor of cdk4 (INK4); cdk4/6; cyclin D
____________________ bind to and inhibit the activities of intact cdk-cyclin complexes
CDK interacting protein (CIP)
___ is a family of activators of genes for DNA replication:
- cell cycle genes (cyclins, cdks)
- pro-growth transcription factor genes
- DNA replication machinery genes (replisome)
- histone genes
E2F
cyclin D represses DNA replication by binding to _______ and ______
degradation of cyclin D is stimulated by continued pro-growth signals
cyclin-D is phosphorylated and exported to the cytoplasm where it is _____________
PCNA (sliding clamp in eukaryotes) and cdk2; polyubiquitinated
progression to S phase requires sufficient active _____________ to activate _________
- cyclin A/cdk2 activation occurs by cyclin E/cdk2-dependent destruction of the cyclin A/cdk2 inhibitor _____
- phosphorylation of Sic1 makes it susceptible to a ubiquitin ligase
cdk2/cyclin E; cyclin A/cdk2; Sic1; ubiquitin ligase
in S phase, replication is initiated by phosphorylation of complex proteins by _______________
cyclin A/cdk 2
