MBS320 Sp26 Exam 4

Cyclin-Dependent Kinase (Cdk)

A family of serine/threonine kinases whose activity requires binding to a cyclin subunit. Cdks drive cell cycle progression by phosphorylating target proteins.

G1-Cyclin

Cyclin active in G1 phase that helps cells commit to the cell cycle (cyclin D in mammals).

G1/S-Cyclin

Cyclin active at the G1/S transition; triggers commitment to DNA replication (cyclin E in mammals).

S-Cyclin

Cyclin active during S phase that drives DNA replication (cyclin A in mammals).

M-Cyclin

Cyclin that drives entry into and progression through mitosis (cyclin B in mammals).

G1-Cdk

Complex of G1-cyclin with its Cdk partner (cyclin D-Cdk4/6), which begins phosphorylating Rb.

G1/S-Cdk Complex

of G1/S-cyclin with its Cdk (cyclin E-Cdk2), which commits the cell to S phase.

S-Cdk

Complex of S-cyclin with its Cdk (cyclin A-Cdk2), which initiates DNA replication at licensed origins.

M-Cdk

Complex of M-cyclin with its Cdk (cyclin B-Cdk1), which triggers entry into mitosis.

MPF2

Maturation (or M-phase) Promoting Factor; the original name for active M-Cdk, discovered in frog eggs.

Cdk-Activating Kinase (CAK)

Kinase that phosphorylates a conserved threonine in the Cdk activation loop, required for full Cdk activity.

Wee1 Kinase

Kinase that phosphorylates inhibitory tyrosine (and threonine) residues on M-Cdk, keeping it inactive until mitotic entry is appropriate.

Cdc25 Phosphatase

Phosphatase that removes the inhibitory phosphates placed by Wee1, switching M-Cdk on and triggering mitosis.

Cyclin-dependent Kinase Inhibitors (CKIs)

Proteins (e.g., p21, p27, p16) that bind and inhibit cyclin-Cdk complexes, blocking cell cycle progression in response to stress or differentiation cues.

SCF

Skp1-Cullin-F-box; an E3 ubiquitin ligase that targets phosphorylated substrates (like the CKI Sic1 / p27) for destruction, especially at the G1→S transition.

APC/C

Anaphase-Promoting Complex/Cyclosome; an E3 ubiquitin ligase that triggers anaphase onset and mitotic exit by tagging securin and M-cyclin for degradation.

Cdc20

An activator of APC/C during mitosis that recruits securin and M-cyclin as substrates.

Ubiquitin Activating Enzyme (E1)

Enzyme that activates ubiquitin in an ATP-dependent step, forming a thioester bond with it.

Ubiquitin Conjugating Enzyme (E2)

Enzyme that receives activated ubiquitin from E1 and works with E3 to transfer it to the substrate.

Ubiquitin Ligase (E3)

Enzyme that recognizes specific substrates and catalyzes transfer of ubiquitin from E2 onto the substrate; provides substrate specificity.

Proteasome

Large multi-subunit protease (26S) that degrades polyubiquitinated proteins into short peptides.

Ras

Small GTPase activated downstream of growth factor receptors; launches the MAP kinase cascade. Commonly mutated in cancers.

MAP-kinase cascade

A three-tiered kinase relay (MAPKKK → MAPKK → MAPK) activated by Ras that phosphorylates transcription factors driving proliferation.

Myc

Transcription factor induced by MAP kinase signaling; activates expression of G1-cyclins and many genes promoting cell growth.

E2F

Transcription factor family that drives expression of S-phase genes (G1/S-cyclin, DNA replication proteins); held inactive by Rb until phosphorylation releases it.

Rb

Retinoblastoma protein; a tumor suppressor that binds and inhibits E2F. Phosphorylation by G1-Cdks releases E2F and permits S-phase entry.

Tumor suppressor

A gene whose product normally restrains proliferation or promotes cell death; loss-of-function mutations contribute to cancer (e.g., Rb, p53).

Protooncogene

A normal gene whose product promotes proliferation; hyperactivating mutations turn it into an oncogene (e.g., normal Ras).

Oncogene

Mutant hyperactive form of a protooncogene that drives unregulated proliferation.

Origin Recognition Complex (ORC)

Six-subunit complex bound to replication origins that serves as the platform for assembling the pre-replicative complex.

Cdc6

Protein that binds ORC and, with Cdt1, recruits the MCM helicase to origins.

MCM - DNA Helicase

Minichromosome Maintenance complex (MCM2-7); the replicative helicase that unwinds DNA at replication forks once activated in S phase.

Pre-Replicative Complex (PreRC)

Assembly of ORC + Cdc6 + Cdt1 + MCM at origins during G1; licenses origins. S-Cdk activates licensed origins and simultaneously blocks re-licensing, ensuring DNA is replicated once per cycle.

Telomere

Repetitive DNA sequence at chromosome ends that protects them from degradation and from being recognized as double-strand breaks.

Centromere

The constricted chromosomal region where sister chromatids are joined and where the kinetochore assembles.

Chromatid

One of the two identical copies of a replicated chromosome, joined to its sister at the centromere by cohesin.

Homologous chromosomes

Pair of chromosomes (one from each parent) carrying the same genes in the same order, but possibly different alleles.

Kinetochore

Large protein complex assembled on each sister centromere that attaches the chromosome to spindle microtubules.

Cohesin

Ring-shaped complex that holds sister chromatids together from S phase until separase cleaves it at anaphase.

Condensin

Ring-shaped complex related to cohesin that compacts chromosomes during mitosis.

Smc

Structural Maintenance of Chromosomes; family of ATPase proteins forming the core of cohesin and condensin rings.

Centrosome

Main microtubule-organizing center (MTOC) of animal cells; nucleates the mitotic spindle. Contains a pair of centrioles surrounded by pericentriolar material.

Centriole

Cylindrical structure of nine triplet microtubules; two centrioles form the core of each centrosome.

Lamin

Intermediate filament protein that forms the nuclear lamina lining the inner nuclear membrane; phosphorylation by M-Cdk triggers its disassembly.

Nuclear Envelope

Double membrane surrounding the nucleus, continuous with the ER and perforated by nuclear pore complexes.

Nuclear Envelope Breakdown

Disassembly of the nuclear envelope at prometaphase, triggered by M-Cdk phosphorylation of lamins and nuclear pore proteins.

Ran

Small GTPase that regulates nucleocytoplasmic transport in interphase and helps promote spindle assembly around chromosomes in mitosis.

RanGEF

Ran Guanine nucleotide Exchange Factor (RCC1); chromatin-bound, generates Ran-GTP near chromosomes.

RanGAP

Ran GTPase-Activating Protein; cytoplasmic, hydrolyzes Ran-GTP to Ran-GDP, establishing the Ran gradient.

Dynein

Minus-end-directed microtubule motor; among other jobs, pulls on astral microtubules to position spindle poles and contributes to anaphase B.

Plus-end directed Kinesin-Related Protein ((+)KRP)

Kinesin that walks toward microtubule plus ends; slides antiparallel overlap microtubules apart to push spindle poles away from each other (anaphase B).

Minus-end directed Kinesin-Related Protein ((-)KRP)

Kinesin that walks toward minus ends; helps focus microtubule minus ends at the spindle poles.

Chromokinesin

Plus-end-directed kinesin that binds chromosome arms and generates polar ejection forces pushing chromosomes away from the poles, helping alignment at the metaphase plate.

Kinetochore Microtubule

Spindle microtubule whose plus end is attached to a kinetochore; moves chromosomes during mitosis.

Overlap or Polar Microtubule

Microtubules from opposite poles that interdigitate in the spindle midzone; sliding apart drives anaphase B.

Astral Microtubule

Microtubules radiating outward from spindle poles toward the cell cortex; position and orient the spindle.

Treadmilling

Steady-state behavior in which subunits add at one end of a polymer while being lost from the other end at the same rate, so the polymer appears to move without changing length.

Spindle Pole

Focal point at each end of the mitotic spindle where microtubule minus ends converge, typically organized by a centrosome in animal cells.

Securin

Inhibitor that binds and restrains separase during metaphase; ubiquitinated by APC/C-Cdc20 and degraded at the metaphase-to-anaphase transition.

Separase

Protease that, once freed from securin, cleaves the Scc1/kleisin subunit of cohesin so sister chromatids can separate.

Prophase

Chromatin condenses into visible chromosomes and the mitotic spindle begins to assemble; nuclear envelope still intact.

Prometaphase

Nuclear envelope breaks down; kinetochores capture spindle microtubules and chromosomes begin congressing.

Metaphase

Chromosomes are aligned at the metaphase plate with sister kinetochores attached to microtubules from opposite poles (biorientation).

Anaphase

A Sister chromatids separate and move poleward as kinetochore microtubules shorten.

Anaphase B

Spindle poles themselves move farther apart, elongating the cell via overlap microtubule sliding and astral microtubule pulling.

Telophase

Chromosomes arrive at the poles, nuclear envelopes reform around each set, chromosomes decondense, and the spindle disassembles.

Cytokinesis

Division of the cytoplasm, producing two daughter cells; in animal cells by contraction of an actin-myosin ring.

G1-Checkpoint

Late-G1 checkpoint (the restriction point in mammals) that assesses DNA damage, cell size, and growth signals before commitment to S phase.

G2-Checkpoint

Checkpoint in G2 that blocks entry into mitosis if DNA is damaged or incompletely replicated, largely by keeping M-Cdk inhibited (Wee1 active, Cdc25 inhibited).

Metaphase Checkpoint

Also called the spindle assembly checkpoint; delays anaphase onset until every kinetochore has made a proper bipolar attachment, by inhibiting APC/C-Cdc20.

p53

Transcription factor and tumor suppressor stabilized by DNA damage; induces p21 (a CKI) to arrest the cell cycle or induces apoptosis. One of the most frequently mutated genes in human cancers.

Mdm2

E3 ubiquitin ligase that targets p53 for degradation in unstressed cells, keeping p53 levels low.

Mad2

Spindle assembly checkpoint component; recruited to unattached kinetochores, where it helps sequester Cdc20 and block APC/C activity until attachments are complete.

Aurora B Kinase

Kinase of the chromosomal passenger complex that destabilizes incorrect (non-bipolar) kinetochore-microtubule attachments so they can be re-made correctly.

Ndc80 (Ncd80)

Kinetochore complex that forms the main load-bearing attachment between kinetochores and microtubule plus ends.

Microtubule Stabilizing and Destabilizing Factors

Regulators of microtubule dynamics. Stabilizers (e.g., +TIPs like EB1, XMAP215/ch-TOG) promote growth; destabilizers (e.g., kinesin-13/MCAK, stathmin/Op18) promote catastrophe and shrinkage.

Actin-Myosin Contractile Ring

Ring of actin filaments and bipolar myosin II filaments assembled at the cell equator; its contraction drives cleavage.

Cleavage Furrow

The indentation of the plasma membrane produced as the contractile ring constricts, eventually pinching the cell in two.