BIO 201 Lecture Notes - Lecture 26: Tumor Suppressor Gene, E2F, Restriction Point
6 Sep 2018
School
Department
Course
Professor
Bio 201
Lara Hutson
Lecture 26: Cell Cycle Checkpoints (Ch. 11, pp. 205-211)
Overview
- Cell cycle checkpoints
- Tumor suppressor genes
- Oncogenes and proto-oncogenes
Cell cycle checkpoints: control mechanism used by eukaryotic cells to ensure that cells proliferate only
when certain internal and external condition are met. Checkpoints are regulated by many different
“sentinel” systems that monitor nutrients, growth factors, cell size, DNA damage, and tension.
MPF: Maturation-promoting factor, is the Cyclin-Cdk complex that was discovered first in frog egg. It
stimulates the mitotic and meiotic phase of the cell ccle
Multiple cell cycle checkpoints
G1/S is the restriction point
- The G1/S checkpoint is referred to as the restriction point because it is the “point of no return”
for proliferation
-
When checkpoints fail, it can lead to excessive proliferation of cells
- Excessive proliferation can lead to cancer
- Cancer = over 200 distinct diseases
- Main causes
o Mutations
▪ Tumor suppressor genes – Rb and p53
▪ Proto-oncogenes – ras
o Viruses
Tumor suppressor genes: genes whose normal protein products act to prevent cell cycle progression
- Loss-of-function mutations inactivate protein, causing progression through cell cycle at
inappropriate times.
Tumor-suppressor genes: Retinoblastoma (Rb)
- Cancer of the retina
- Caused by mutation in Rb gene
- Rb is also the name of the protein product
- Rb protein prevents cells from entering S phase (G1/s checkpoint)
Rb function
Unstimulated:
Rb binds to transcription factor E2F preventing transcription of S-phase genes.
Growth factors:
1. Activation of ras pathway
2. Transcription of S-phase cyclin → activates a Cdk
3. Cdk phosphorylates Rb
4. Rb falls off E2F → S-phase gene transcription
- Proteins involved in DNA replication.
Rb mutations
1. Rb mutations prevent Rb from binding to E2F
2. Growth factor-independent activation of E2F
3. E2F constitutively active → uncontrolled proliferation.
4.
Document Summary
Cell cycle checkpoints: control mechanism used by eukaryotic cells to ensure that cells proliferate only when certain internal and external condition are met. Checkpoints are regulated by many different (cid:862)se(cid:374)ti(cid:374)el(cid:863) syste(cid:373)s that (cid:373)o(cid:374)itor (cid:374)utrie(cid:374)ts, growth fa(cid:272)tors, (cid:272)ell size, dna damage, and tension. Mpf: maturation-promoting factor, is the cyclin-cdk complex that was discovered first in frog egg. It stimulates the mitotic and meiotic phase of the cell ccle. The g1/s (cid:272)he(cid:272)kpoi(cid:374)t is referred to as the restri(cid:272)tio(cid:374) poi(cid:374)t (cid:271)e(cid:272)ause it is the (cid:862)poi(cid:374)t of (cid:374)o retur(cid:374)(cid:863) for proliferation. When checkpoints fail, it can lead to excessive proliferation of cells. Main causes: mutations, tumor suppressor genes rb and p53, proto-oncogenes ras, viruses. Tumor suppressor genes: genes whose normal protein products act to prevent cell cycle progression. Loss-of-function mutations inactivate protein, causing progression through cell cycle at inappropriate times. Rb is also the name of the protein product. Rb protein prevents cells from entering s phase (g1/s checkpoint)
