Cell Bio-The Cell Cycle.txt

  1. The action of growth factors results in...
    the activation of the cell cycle, aka cell division
  2. Major regulatory events of the cell cycle occur during _____.
    G1 phase
  3. Term used to describe once the fact that once the cell is differentiated, it is committed and can't go back.
    terminal differentiation
  4. The __________ checkpoint controls the expression of genes required for the cell to progress into S phase.
    G1/S phase
  5. The ______ checkpoint controls the expression of genes that function in nucleotide synthesis and DNA replication.
    S phase
  6. The ______ checkpoint controls the assembly of the mitotic spindle in preparation for mitosis.
    G2/M phase
  7. Cell cycle checkpoint reactions are mediated by ______.
  8. The cyclin of a cyclin:CDK complex is the ______ component and the CDK is the _______ component.
    regulatory; catalytic
  9. CDK is only active and catalytic when...
    it is complexed with cycllin
  10. CDKs are generally present throughout the cell cycle, but they are not always active because...
    cyclins required to activate them are only present at very specific times.
  11. During the mid/late G1 phase, cyclin D-CDK4/6 function as a ______ to perform the following function...
    kinase; phosphorylate an inactivate the retinoblastoma protein (Rb).
  12. Phosphorylation and inactivation of Rb by cyclin D-CDK4/6 is a key step in...
    the progression through G1 to S phase.
  13. During the late G1/S phase, cyclinE-CDK2 functions as a _____ to perform the following function...
    kinase; phosphorylates and inactivates Rb protein and other proteins.
  14. Phosphorylation and inactivation of Rb by cyclin E-CDK2 is important to facilitate...
    progression through late G1 and S phases.
  15. During the S/G2 phase, cyclinA-CDK2 functions as a ______ to perform the following function...
    kinase; phosphorylates and activates proteins that function in DNA replication.
  16. During G2/M phase, cyclin B-CDK1 functions as a ______ to perform the following function...
    kinase; phosphorylates and activates proteins that function in mitosis/cytokinesis.
  17. Phosphorylation of Rb by the cyclin D1:CDK4/6 complex induces.....
    a conformational change that causes Rb to release E2F (transcription factor).
  18. Major regulator of cell cycle progression.
    retinoblastoma protein (Rb)
  19. Rb is active when it is _____.
  20. Active Rb __________ the progression of the cell cycle.
    inhibits or blocks
  21. 80% of all tumors show defects in the ________.
    Rb pathway
  22. Transcription factor that binds DNA at a site that is found in the promoter regions of genes that function in cell cycle regulation.
  23. Rb is ______ in G0 and early/mid G1; it is _____ and couple with ____.
    unphosphorylated; active; E2F
  24. Rb has what function on E2F, when it is active and bound?
    represses the E2F transcriptional activation function
  25. When Rb is phosphorylated by ______, it is _____ and...
    cyclin:cdk; inactivated; it releases E2F
  26. E2F has what function?
    turns on the expression of itself and cyclin E, which progresses the cell cycle into the next phase, S phase
  27. proteins that stop, clock, or inhibit cell cycle progression.
    cyclin dependent kinase inhibitors (CDKIs)
  28. Family of CDKIs known as "inhibitor of kinase" that have a specific target.
    Ink family
  29. Family of CDKIs known as "cyclin inhibitor protein/ kinase inhibitor protein" that have a much broader specificity.
    Cip/Kip family
  30. How are CDKIs associated with many cancers?
    these proteins are the brakes of the cell cycle; if they are aberrant, the cell cycle will continue without abandon
  31. When kinases are inactivated by CDKIs,...
    Rb remains active, E2F is blocked, and the cell cycle cannot progress
  32. The genes that encode the CDKIs are induced in response to ________, such as... (3)
    growth inhibitory signals; soluble growth inhibitors (cytokines), contact inhibition, and DNA damaging agents
  33. Mutations in CDKIs are _______, causing ______, therefore _____.
    loss-of-function; uninhibited growth; cancer.
  34. The specific sequences at which DNA is opened by helicases.
    origin of replication
  35. Enzyme the separates the two DNA strands prior to replication.
  36. The site of DNA replication, including the ssDNA and the protein complex that is replicating it.
    replication fork
  37. The leading strand is replicated in a _____manner directly behind ____.
    continuous; the helicase
  38. Enzymes that synthesize DNA
    DNA polymerases
  39. To produce a complementary strand, polymerase/primase binds to the replication fork and...
    synthesizes an RNA primer
  40. After primase synthesizes the primer, _____ binds to the primer and extends it.
    DNA polymerase
  41. Enzyme that degrades RNA primer.
    RNase H
  42. Enzyme that seals the gaps of DNA.
    DNA ligase
  43. Defective DNA replication or defective DNA results in ____.
  44. How do anti-cancer drugs work?
    They disrupt the cancerous DNA, the cell tries to fix it and fails, then apoptosis takes place and cancer cells die
  45. Apoptosis is define morphologically by...
    cell shrinkage and nuclear disintegration
  46. Apoptotic bodies are phagocytiized by________.
    neighboring cells and macrophages
  47. Apoptosis results in...
    cell elimination without inflammation
  48. Plasma membrane enclosed fragments of cells.
    apoptotic bodies
  49. In the immune system, apoptosis functions to...
    eliminate self-reactive clones
  50. In mammary gland biology, apoptosis function in...
    post-lactational mammary gland involution
  51. Pathological cell death
  52. Necrosis is cell death due to...
    extreme biological insult
  53. Necrosis causes an _________.
    inflammatory response
  54. As a result of necrosis, the cell explodes, releasing...
    large antigenic molecules that induce inflammation
  55. The extrinsic apoptosis pathway is activated by a _____.
    extrinsic death signal
  56. The intrinsic apoptosis pathway that is activated by ______ and requires ______; sometimes also called the ______.
    DNA damage; functional p53; mitochondrial pathway
  57. enzymes that cleave or break down proteins.
  58. When you degrade actin, _______ occurs.
  59. When the l=death signal ligand binds to its receptor, the ________ is activates.
    DISC formation (death inducing signaling complex)
  60. DISC activates _____.
    initiator caspases
  61. Initiator caspases digest....
    cytoplasmic structural proteins and translocase
  62. When initiator caspases digest cytoplasmic structural proteins, _____ occurs.
  63. Initiator caspases digestion of translocase results in...
    improper positioning of phosphatidylserine in the plasma membrane
  64. What is the early signal to neighboring cells to initiate phagocytosis?
    phosphatidylserine being positioned on the outer plasma membrane
  65. How are execution caspases activated?
    initiator caspases cleave and interact with APAFs (apoptotic protease activating factors)
  66. APAF contain...
    cytoplasmic proteins and cytochrome c
  67. _______ is responsible for full activation of the apoptosis program
    cytochrome c
  68. Under normal condition, cytochrome c is located in ________, and kept there by the protein ______.
    mitochondria; Bcl-2
  69. ______ cleave BID to active tBID, which migrates to the mitochondria to form......
    initiator caspases; a channel that facilitates cytochrome c leakage int the cytoplasm, which activates execution caspases and apoptosis
  70. tBID is activated by ____; tBID deactivates _____, allowing _________, which causes leakage of ______ into the cytoplasm, activating ____ and ultimately _______.
    BID; Bcl-2; pores to form in the mitochondrial membrane; cytochrome c; execution caspases; extrinsic apoptosis
  71. Execution caspases result in ____, which are phagocytized by neighboring cells.
    apoptotic bodies
  72. Autophagy is induced by _______, such as... (2)
    cellular stress; nutrient starvation and growth factor deprivation
  73. Autophagy provides the cell with _____ (2) in order to...
    carbons from amino acids and fatty acids for generation of ATP; prolong life
  74. In the autophagy pathway, metabolic stress induces the formation of ...
    an isolation membrane surrounding cytoplasmic components or organelles.
  75. The autophagosome fuses with a ________,which....
    lysosome; promotes degradation or digestion of cell components.
  76. The result of digestion within the autolysosome is....
    generation of energy (ATP) and protein synthesis
  77. How is apoptosis useful in medicine?
    treat allergies by killing WBCs (basophils and eosinophils with histamines) and chemotherapy (causing DNA damage to initiate intrinsic apoptosis)
  78. p53 is activated in the ____ in response to ______; its function is...
    nucleus; DNA damage; encodes a protein that activates transcription
  79. p53 is activated by ______.
  80. What is the biological scenario of p53 function?
    moderate DNNA damage activates a limited number of kinases that phosphorylate and activate p53; limited transcriptional activation results in increased p21 expression, cell cycle arrest, and DNA REPAIR!!!
  81. p53 induces ______.
  82. How does medicine exploit p53?
    Cause extensive DNA damage to maximally activate kinases to phosphorylate p53; extensive activation of p53, resulting in APOPTOSIS (damage cannot be repaired).
  83. p21 functions as a _____, which means...
    CDKI; it blocks the function of a cyclin:CDK, blocking phosphorylation of Rb, thus blocking cell cycle progression into S phase (PREVENTS REPLICATION OF DAMAGED DNA).
  84. With extensive DNA damage (ie. chemotherapy), p53 activates _____ via _____.
    apoptosis; the intrinsic apoptotic pathway
  85. With extensive DNA damage, the protein ______ detects the damage; this protein in turn activates ______, which phosphorylates p53.
    ATM; Chk2
  86. When p53 is phosphorylated by ______, it increases transcription of _____, a pro-apoptotic gene.
    Chk2; Bax
  87. Once Bax is activated by p53, it performs the following function....
    inserts in outer mitochondrial membrane, creating pores and allowing leaking of cytochrome c into the cytoplasm (which activates execution caspases, resulting in apoptosis).
  88. Cytochrome c forms a complex with ______ to activate _____.
    APAFs; execution caspases
  89. ________ mutations in p53 are common in _____.
    loss-of-function; cancers
  90. Why is loss of function of p53 detrimental?
    it is inactivation of the p53 mediated response to DNA damage, so damaged DNA may be replicated; also, cancer cells with a mutated p53 will not respond to chemotherapy.
  91. The transactivation domain of p53 performs what function?
    promotes transcription by interacting with transcriptional co-activators
  92. What is the critical domain of p53 and what is its function?
    The DNA-binding domain; mediates transcriptional activation by binding to the gene promoters
  93. Most inactivating mutations in p53 occur in the ______.
    DNA-binding domain
  94. If the drug Herceptin targets ERBB2, an EGFR, how is it useful in treating breast cancer?
    An EGFR is an RTK; breast cancer is associated with HER2 and HER3; the ligand (Heregulin) binds to HER3, which dimerizes with HER2; this causes activation of the intracellular kinase domain, MAPK of HER2; This kinase activity is a potent growth-promoting factor; if you shut off the extracellular receptor, you can stop cell growth.
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Cell Bio-The Cell Cycle.txt