Regulation Continued 10/18/2012
MPF = maturation promoting factors
Which includes CdKs (cyclin dependent
kinases involved in phosphorylation of
proteins involved in mitosis) p53 is a protein that blocks progression into mitosis if
the DNA is damaged. Mutations in this protein are linked
to many cancers.
• Cell growth factors (such as FGF, EGF, Erythropoietin) signal the cell to move through the cycle by
stimulating it to produce active CdKs.
• One of the things required is to remove the inhibition on the expression of certain genes
• The RETINOBLASTOMA protein is abundant in the nucleus of all cells and it prevents certain
proteins from stimulating transcription.
• However, when it is phosphorylated (by a CdK which was activated by a growth factor), it
releases the protein needed for transcription and thus the cell will progress through the cycle. • The inhibition of a cell from continuing through the cell cycle is in part done by Cdk inhibitor proteins.
One of the best understood checkpoints stops the cell in G1 if there is DNA damage (stops it from dividing).
DNA damage > increase in p53 which is a gene regulatory protein
p53 stimulates the transcription of p21 which is Cdk inhibitor protein (Cdk that promotes DNA replication)
P21 binds to Sphase cyclin Cdk complexes (Cdks that allow cell to enter into S phase), blocking their
action, thus inhibiting DNA replication and possibly then leading down the path of DNA repair
In addition to these signals, there are:
Involves cellcell communication when cells are healthy they stop dividing when they make contact with
Cells that are malignant lose sensitivity of contact inhibition and pile on top of each other▯ tumors
Importance of the Extracellular Matrix = ECM in keeping a cell under regulation.
Normal cells will stick to a petri dish, ECM
Malignant cells can separate away and do fine without having an attachment
Cell Cycle Regulation by CdKs
KINASES regulate the
movement through these
Kinases are activated
by the presence of
CYCLINS which vary
in concentration at
various times in the cycle
Cyclins complex with
the kinases to form
CdKs which become active
phosphorylating enzymes G1 Mitosis
By phosphorylating specific
proteins the cell cycle proceeds
EXAMPLE 1: The Retinoblastoma protein –
When phosphorylated, it releases a protein 2
that is bound to it which acts as a transcription
factor thus allowing the progression through the cycle
EXAMPLE 2: DNA damage -à increases in p53
p53 stimulates transcription of p21
p21 binds to and blocks S-phase CdK Meiosis
• Occurs in the Gonads: ovaries and testes
• Fertilization happensZygote is very small cytoplasm is divided into many cells
• Eggs cells and sperm cells known as gametes (germ line cells) – have half of the amount of DNA, only
one chromosome of each kind, have 23 chromosomes
• Haploid is one chromosome of each kind (1N) where n is number of chromosomes (different kinds)
• Diploid is having two of each kind of chromosome (2N)
• Sperm cell is haploid, zygote is diploid
• Results in the generation of four cells that have only one copy of each chromosome (haploid or 1n
chromosomes) and therefore half the genetic material that a somatic cell has after the completion of
mitosis (which is diploid and has 2n chromosomes).
These (1n cells) are the gametes egg and sperm cells
• Requires two consecutive divisions (Meiosis I and Meiosis II) without a significant gap between them.
• The specifics are different in males and females in terms of timing and final gamete numbers.
Comparing Meiosis in Males and Females