Home > Preview
The flashcards below were created by user
on FreezingBlue Flashcards.
- Covalent conjugation attached to lysine residues of substrates.
- E1(activation, needs ATP), E2(conjugation), E3(Ligase, high specificity based on UB signal)
- targeted by multisubunit ATP-dependent protease known as the 26S proteasome for degradation
APC: anaphase-promoting complex
- aka E3 Ligase of ubiquitin, matches to mitotic cyclin destruction box
- Late ANaphase, APC polyubiquitinates mitotic cyclins
- cyclin down, MPF(CDK and cyclin) activity down -> Telophase
- regulator of APC
- Inactivated when phosphorylated by G1 cyclin CDK -> mitotic cyclin increases->promote mitosis entry
- removes the phosphate from Cdh1 late in anaphase to activate APC->polyubiquitation of cyclin
- Lack CDC->no decrease in Cyclin-> long cells
- Overactive CDC-> cyclin cycle too short-> premature telophase
Spindle Pole Body Duplication
Cdk Activity Regulation
- Phosphorylated in order by Wee1 CAK
- Cdc25 phosphotase of P of Wee1 to activate CDk
- No CDC 25-> No MPF activity-> increased G2 elongated cells
- Too much Wee1 -> No MPF activity -> increased G2 elongated cells
- No Wee1-> No inhibition of MPF-> too much mitosis-> premature small cells
- Too much CDC25-> Too much MPF -> too much mitosis-> premature small cells
Cyclin-kinase inhibitors (CKIs)
- two classes:
- CIP (Cdk inhibitory protein)
- INK4 (inhibitors of kinase 4)
- CIP: p21, p27, and p57.
- CIP inhibits all cyclin-Cdk complexes.
- INK4 inhibits only Cdk4/6-cyclin D complexes.
- Binding of CKIs to cyclin-Cdk complexes leads to cell cycle arrest.
phosphorylate nuclear lamins to breakdown nuclear envelope
- APC specificity factor that ubiquinates Securin
- Securin is the muzzle on Separase(pacman) that separtates sister chromatids by cutting Scc1
- different cyclins control different cell cycle stages through restriction points
- Cyclin D->restriction point of G1
E2F transcription factors
- stimulate transcription required for DNA replication, deoxyribonucleotide synthesis as well as Cdk2, cyclin A and cyclin E.
- E2F inhibited by binding of hypophosphorylated Rb protein, a product of tumor-suppressor gene RB.
- G1->S transition requires activation of E2Fs
- Sustained Angiogenesis
- Tissue Invasion and metastasis
- Limitless replication Potential
- Self-sufficent growth signals
- Insensitvity to anti-growth signals
- Evasion of Apotosis
Tumor cell properties
whose products have the ability to transform eukaryotic cells so that they grow in a manner analogous to tumor cells. Oncogenes alone are not sufficient to cause cancer. Inactivation of tumor suppressors is a major event leading to the development of cancer
normal cellular genes known to be progenitors of oncogens
encode proteins that inhibit the progression of tumors.
localized reduplication (gene amplification) of a DNA segment, leading to overexpression of the encoded proteins.
wants to fuck with apoptotic proper sequence by binding to Bax, but Bad prevents that. Bax and Bad are pro-apoptotic.
- Over-expression TGF-alpha, stimulates cell proliferation.
- EGF receptor gene amplification
- Ras mutations
- transcription factor c-Myc which helps regulate cell proliferation is frequently overexpressed
- Anti-apoptosis proteins Bcl-2 overexpression
- Cell cycle control proteins Cyclin D is amplified
- Inactivation of p53(CDK Inhibitor)
- Regulated by post-translational modifications: phosporylation acetylation, ubiquitination
- Regulated by a number of protein factors. MDM2 is a ubiquitin ligase which negatively regulates p53 activity. MDM2 targets p53 for degradation and can repress the transcriptional activity of p53. MDM2 is induced by 53---- a negative feed back control.
- p53 mutation is dominant.
- p53 regulates cell cycle (p21) and apoptosis(Bax)
- Cigarette smoking--> benzopyrene-->metabolic activation-->
- T transversion mutation-->aa 175, 248, 273 mutations-->60% lung cancer containing p53 mutations.
- proto-oncogene encoding a tyrosine kinase
- v-src lacks the C-terminal inhibitory phosphorylation site (tyrosine-527), and is therefore constitutively active as opposed to normal src (c-src)
proto-oncogene whose expression can be enhanced and promoted by viral genes