Important)Informa+on!Review!Session!1:!Thursday!Dec.!10th,!6-8PM!TLS!154!!Review!Session!2!(Last!Day!of!Class):!Friday!Dec.!11th,!1:25PM!Normal!Class!IF!YOU!HAVE!QUESTIONS!ABOUT!THE!EXAMS,!ASK!THEM!BEFORE!THE!END!OF!CLASS!!!Scheduled)Final)Exam:)Wednesday)December)16,)Arjona)Hall;)8:00-10:00;)10:00-12:00;)12:00-2:00,)2:00-4:00.))See)Exam)Registra+on)Link-)You)must)be)registered)and)show)up)at)the)correct)+me!)!!Early/Late!Final!Exam:!TBA!!!!!!Our!HuskyCT!site!is!usually!taken!down!shortly!following!the!end!of!the!semester,!so!you!should!save!or!print!all!course!material!before!then!!!The!professor!and!TA!will!not!have!contact!with!Cell!Biology!students!a^er!Dec!11th,!and!you!may!not!discuss!Exam!content!with!any!other!students!during!finals!week!!FOR) THOSE) OF) YOU) WITH) PERMISSION)FROM) DOS) TO) TAKE) AN) ALTERNATIVE)EXAM,) BE) SURE) TO) CONFIRM) THE) EXAM)TIME)AND)PLACE)WITH)THE)COURSE)TA.)Cancer)Cells)))Please)take)some)+me)to)fill)out)the)online)evalua+ons)for)the)course.))You)may)have)a)chance)to)do)this) at)the)end)of)Wednesday’s)class.))Alterna+vely,)you)can)complete)the)survey)on)your)own)+me.))Course)Evalua+ons)Last)Class:))Secre+on)Systems,)Adhesins,)Effectors,)and)Toxins)EHEC 2.!In`mate!Adherence!3.!Pedestal!Assembly!1.!Type!III!Effector!Transloca`on!EHEC EHEC In`min!Tir!EspFU!>50!Esps!X!PM!Host!Cell!In`min-mediated!clustering!of!Tir!EspFU-mediated!signaling!and!ac`n!assembly!T3SS!4.!Intoxica`on!StxAB!Ribosome!inac`va`on!&!cell!death!An)overview)of)cell)changes)that)cause)cancer!Cancer!causes!roughly!one-fi^h!of!the!deaths!in!the!US!each!year.!Carcinomas!are!cancers!that!arise!from!epithelial!cells!and!are!the!most!common!cancers!in!humans.!Sarcomas!arise!from!connec`ve!or!muscle!`ssues.!Leukemias!and!lymphomas!arise!from!blood!cells.!Figure 20-2 Molecular Biology of the Cell Several!fundamental!cellular!proper`es!are!altered!during!carcinogenesis!(the!genera`on!of!cancer).!!Cancer!cells!break!the!most!basic!rules!of!cell!behavior!that!build!and!maintain!organisms.!!The!study!of!today’s!topic!–!cancer!biology!–!has!led!to!many!discoveries!in!the!field!of!cell!biology:!numerous!proteins!have!been!iden`fied!because!abnormali`es!in!their!func`on!can!lead!to!uncontrolled!cell!growth,!increased!cell!division,!decreased!cell!death,!enhanced!cell!migra`on,!etc.!These!proteins!are!involved!in!DNA!repair,!cell!signaling,!cell!cycle!control,!cell!growth,!programmed!cell!death,!cytoskeletal!rearrangements,!and!`ssue!architecture.!Cancer)cells)are)highly)replica+ve)and)invasive!Cancer)cells)are!defined!by!two!heritable!proper`es:!(1)!they!reproduce!in!defiance!of!the!normal!restraints!on!cell!growth!and!division,!and!(2)!they!invade!and!colonize!territories!normally!reserved!for!other!cells.!!A!normal!cell!that!grows!and!proliferates!out!of!control!will!give!rise!to!a!tumor!–!new!growth!(neoplasm).!If!the!neoplas`c!cells!are!not!invasive,!they!are!considered!benign.!A!tumor!is!considered!a!cancer!if!it!is!malignant!–!if!its!cells!have!acquired!the!ability!to!invade!other!`ssues.!This!invasiveness!or!spread!of!cancer!cells!is!called!metastasis.!!!!!!!!!Cancer!cells!contain!soma`c!muta`ons.!These!muta`ons!can!be!triggered!by!chemical!carcinogens!or!from!radia`on.!Some!cancers!are!also!caused!by!viruses.!Cancers!can!arise!from!the!inheritance!of!mutant!genes!that!predispose!cells!for!accumulated!soma`c!muta`ons.!!MBoC!Most!cancers!derive!from!a!single!abnormal!cell,!and!even!when!a!cancer!has!metastasized,!its!origins!can!usually!be!traced!to!a!primary!tumor!in!a!specific!organ.!The!primary!tumor!is!derived!from!division!of!a!single!cell!that!ini`ally!experienced!some!heritable!change.!Subsequently,!addi`onal!changes!accumulate!in!the!descendants!of!this!cell,!allowing!them!to!out-grow,!out-divide,!and!out-live!their!neighbors.!!!Henrieia!Lacks!Figure 20-9 Molecular Biology of the Cell (© Garland Science 2008) Stages)of)the)progression)of)an)epithelial)cancer)of)the)cervix!Genes)important)in)the)ini+a+on)of)cancer:)proto-oncogenes,)tumor-suppressor)g enes,))))and)caretaker)genes))All!of!the!informa`on!in!this!table!is!important.!(GOF))(LOF))(LOF))Many)factors)control)growth)and)prolifera+on!Caretaker)genes)encode!proteins!involved!in!DNA!repair.!!Proto-oncogenes!and!tumor-suppressor)genes!encode!many!members!of!the!classes!of!factors!that!are!shown!in!this!figure.!Whether!a!signaling!protein!is!a!tumor!suppressor!or!proto-oncogene!really!depends!on!whether!its!pathway!normally!inhibits!or!promotes!growth!and!prolifera`on.!!!Caretaker)genes)with!LOF!muta`ons!contribute!to!cancer.!)Proto-oncogenes)with!GOF!muta`ons!contribute!to!cancer.!!Tumor-suppressor)genes)with!LOF!muta`ons!contribute!to!cancer.!!DNA)repair)defects)give)rise)to)hereditary)cancers!Loss-of-func+on)muta+ons)in)tumor -suppressor)genes)promote)cancer!Tumor-suppressor)genes!encode!proteins!that!inhibit!cell!prolifera`on!by!several!mechanisms.!Prominent!tumor-suppressors!include:!(1) Proteins!that!regulate!or!inhibit!cell!cycle!progression!(e.g.,!Rb!is!a!protein!that!inhibits!progression!from!G1!to!S);!(2) Receptors!or!signal!transducers!for!hormones!or!developmental!signals!(e.g.,!TGF-β);!(3) Checkpoint!control!proteins!that!arrest!the!cell!cycle!if!DNA!is!damaged!or!chromosomes!are!abnormal!(e.g.,!p53!is!“the!guardian!of!the!genome”);!(4) Proteins!that!promote!apoptosis!–!programmed!cell!death;!(5) Enzymes!that!func`on!in!DNA!repair!which!are!encoded!by!caretaker!genes.!Rb)regulates)the)G1-S)restric+on)point!(S-phase))Unphosphorylated!Rb!binds!to!E2F!transcrip`on!factors!to!prevent!ac`va`on!of!many!genes!required!for!DNA!synthesis!(e.g.,!DNA!polymerases).!CyclinD-CDK4!phosphorylates!Rb.!Phosphorylated)Rb)releases!E2F,!thereby!ac`va`ng!transcrip`on!of!genes!required!for!S-phase.!Overproduc`on!of!CyclinD,!loss!of!p16,!or!loss!of!Rb!is!common!in!human!cancers.!(free))An)(old-school))approach)to)iden+fy)oncogenes)that)transform)
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