transcription of cell cycle genes, allowing cells to traverse the G 1 /S inter-
face.Mutations in Rb occur in tumors;a mutation has the same effect as
inactivating Rb leading to uncontrolled cell proliferation as E2F trancribes
cell cycle genes. p53 is a protective geneor molecular policeman, which
prevents the replication of damaged DNA and stimulates repair. p53 acts as
a transcription factor and also works through the Cdk inhibitors to arrest
the cell cycle at the G 1 /S interface. p53 mutations are found in many
human tumors.
INTRACELLULAR TRAFFICKINGThe key event in exocytosis is translocation of newly synthesized protein
into the cisternal space of the rough ER (signal hypothesis). Proteins and
lipids reach the Golgi apparatus by vesicular transport. Using carbohydrate-
sorting signals, proteins are sorted from the trans-face of the Golgi appara-
tus to secretory vesicles, the cell membrane, and lysosomes.Lysosomal
enzymes are sorted by using a mannose-6-phosphatesignal recognized by
a receptor on the lysosomal membrane. Absence of mannose 6-phosphate
results in default to the secretory pathway and release of enzymes by
exocytosis.Nuclear and mitochondrial-sorting signals (positively charged
amino acid sequences) are recognized by those organelles.
Endocytosisinvolves transport from the cell membrane to lysosomes
using endosome intermediates. The process originates with a clathrin-
coated pitthat invaginates to form a coated vesiclethat fuses with an
endosome.This internalization can be receptor-mediated(e.g., uptake of
cholesterol). Endosomes subsequently fuse with lysosomes. Internalized
receptor/ligand complexes may be conserved, degraded, or recycled.
EPITHELIUMEpithelial cells line the free external and internal surfaces of the body.
Epithelia have a paucity of intercellular substance and are interconnected
byjunctional complexes.Components of the junctional complex include
thezonula occludens(tight junction), which prevents leakage between the
adjoining cells and maintains apical/basolateral polarity; zonula adherens,
which links the actin networks within adjacent cells; and macula adherens
(desmosome), which links the intermediate filament networks of adjacent
cells. Epithelial cells also form a firm attachment to the basal lamina,which
they secrete. Gap junctionsornexipermit passage of small molecules
18 Anatomy, Histology, and Cell Biology