Regulators of
Cell Cycle Progression
The cell cycle, which regulates cell growth
and division, is a highly controlled process. It consists of a sequence of
processes, including mitosis (M phase) and interphase (G1, S, and G2 phases),
which result in cell division. Several molecules and checkpoints carefully
govern the advancement through these phases to guarantee accurate and
error-free cell division. Here is a thorough rundown of the main controllers of
cell cycle progression:
1) Cyclins:
• A class of proteins known as cyclins
experience concentration changes over the course of the cell cycle.
• They create cyclin-CDK complexes by binding
to and activating cyclin-dependent kinases (CDKs).
• Different cyclins are associated with
specific phases of the cell cycle. For example, cyclin D is involved in G1,
cyclin E in the G1/S transition, cyclin A in the S phase, and cyclin B in the
G2 and M phase.
• Target proteins are phosphorylated by
cyclin-CDK complexes to advance the cell cycle.
2) Cyclin-Dependent Kinases (CDKs):
• Serine/threonine kinases called CDKs must
bind to cyclin in order to be activated.
• Phosphorylation and dephosphorylation
reactions control CDK activity.
• When CDKs are active, they phosphorylate a
variety of substrates, including proteins involved in DNA replication,
chromosomal condensation, and cell cycle checkpoints.
3) Retinoblastoma Protein (Rb):
• Rb is a protein that suppresses tumors and
is essential for controlling the G1 phase of the cell cycle.
• Rb interacts with and inhibits the function
of E2F transcription factors in its unphosphorylated state.
• Rb is phosphorylated by CDK-cyclin
complexes, which causes it to become inactive and release E2F, permitting
transcription of the genes needed for DNA synthesis.
4) Checkpoints:
• Cell cycle checkpoints are regulatory
systems that guarantee DNA integrity and appropriate cell cycle progression.
• The G1 checkpoint determines if conditions
are favorable for cell division and checks for DNA damage.
• Before initiating mitosis, the G2
checkpoint monitors DNA replication and looks for any mistakes.
• Chromosome alignment on the metaphase plate
is monitored by the spindle checkpoint during mitosis.
• Checkpoints involve proteins like p53,
ATM/ATR, and CHK1/CHK2, which, in response to abnormalities, can initiate cell
cycle arrest or death.
5) DNA Damage Response:
• Before starting the cell cycle, cells have
systems in place to identify DNA damage and repair it.
• When DNA is damaged, ATM and ATR kinases
become active and phosphorylate downstream targets to stop the cell cycle.
• The coordination of DNA repair and cell
cycle arrest is facilitated by DNA repair proteins including BRCA1 and p53.
6) Anaphase-Promoting Complex/Cyclosome (APC/C):
• The huge protein complex known as APC/C
controls the change from metaphase to anaphase during mitosis.
• It permits sister chromatids to split by
designating particular proteins (such as securin and cyclin B) for destruction
by the proteasome.
7) Mitotic Checkpoints:
• Before anaphase starts, the spindle
assembly checkpoint makes sure that all chromosomes are securely connected to
the spindle.
• Important elements of this checkpoint
include the proteins Mad1, Mad2, Bub1, and BubR1.
8) Growth-related factors and outside signals
• Cell cycle progression can be impacted by
external signals from growth factors and the cellular environment.
• Cell cycle entrance can be induced or
prevented by signaling pathways like the MAPK and PI3K/Akt pathways.
Overall, cyclins, CDKs, checkpoint proteins,
and external signals interact to carefully regulate the cell cycle, ensuring
proper cell division and maintaining genetic stability. Cancer is one of
several disorders that can result from the dysregulation of these regulators.
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