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399456 occurrences (No.44 in the rank) during 5 years in the PubMed. [cache]
32) These results advance our understanding of the control of replication-phase entry and genomic integrity, and identify the AMBRA1-cyclin D pathway as a crucial cell-cycle-regulatory mechanism that is deeply interconnected with genomic stability in embryonic development and tumorigenesis.
* AMBRA1 regulates cyclin D to guard S-phase entry and genomic integrity.
- Mammalian development, adult tissue homeostasis and the avoidance of severe diseases including cancer require a properly orchestrated cell cycle, as well as error-free genome maintenance. The key cell-fate decision to replicate the genome is controlled by two major signalling pathways that act in parallel-the MYC pathway and the cyclin D-cyclin-dependent kinase (CDK)-retinoblastoma protein (RB) pathway1,2. Both MYC and the cyclin D-CDK-RB axis are commonly deregulated in cancer, and this is associated with increased genomic instability. The autophagic tumour-suppressor protein AMBRA1 has been linked to the control of cell proliferation, but the underlying molecular mechanisms remain poorly understood. Here we show that AMBRA1 is an upstream master regulator of the transition from G1 to S phase and thereby prevents replication stress. Using a combination of cell and molecular approaches and in vivo models, we reveal that AMBRA1 regulates the abundance of D-type cyclins by mediating their degradation. Furthermore, by controlling the transition from G1 to S phase, AMBRA1 helps to maintain genomic integrity during DNA replication, which counteracts developmental abnormalities and tumour growth. Finally, we identify the CHK1 kinase as a potential therapeutic target in AMBRA1-deficient tumours. These results advance our understanding of the control of replication-phase entry and genomic integrity, and identify the AMBRA1-cyclin D pathway as a crucial cell-cycle-regulatory mechanism that is deeply interconnected with genomic stability in embryonic development and tumorigenesis.
=>1.管理する, 制御する, 統制する, 抑える, 2.コントロール, 実験対象, 管理, 対照標準
Overview of noun control
The noun control has 11 senses (first 9 from tagged texts)
1. (19) control -- (power to direct or determine; "under control")
2. (16) control -- (a relation of constraint of one entity (thing or person or group) by another;
"measures for the control of disease"; "they instituted controls over drinking on campus")
3. (7) control -- ((physiology) regulation or maintenance of a function or action or reflex etc;
"the timing and control of his movements were unimpaired"; "he had lost control of his sphincters")
4. (5) control condition, control -- (a standard against which other conditions can be compared in a
scientific experiment; "the control condition was inappropriate for the conclusions he wished to
draw")
5. (5) control -- (the activity of managing or exerting control over something; "the control of the
mob by the police was admirable")
6. (4) dominance, ascendance, ascendence, ascendancy, ascendency, control -- (the state that exists
when one person or group has power over another; "her apparent dominance of her husband was really
her attempt to make him pay attention to her")
7. (3) restraint, control -- (discipline in personal and social activities; "he was a model of
polite restraint"; "she never lost control of herself")
8. (2) command, control, mastery -- (great skillfulness and knowledge of some subject or activity;
"a good command of French")
9. (1) control, controller -- (a mechanism that controls the operation of a machine; "the speed
controller on his turntable was not working properly"; "I turned the controls over to her")
10. control -- (a spiritual agency that is assumed to assist the medium during a seance)
11. control -- (the economic policy of controlling or limiting or curbing prices or wages etc.;
"they wanted to repeal all the legislation that imposed economic controls")
Overview of verb control
The verb control has 8 senses (first 4 from tagged texts)
1. (28) control, command -- (exercise authoritative control or power over; "control the budget";
"Command the military forces")
2. (20) control, hold in, hold, contain, check, curb, moderate -- (lessen the intensity of; temper;
hold in restraint; hold or keep within limits; "moderate your alcohol intake"; "hold your tongue";
"hold your temper"; "control your anger")
3. (7) operate, control -- (handle and cause to function; "do not operate machinery after imbibing
alcohol"; "control the lever")
4. (1) manipulate, keep in line, control -- (control (others or oneself) or influence skillfully,
usually to one's advantage; "She manipulates her boss"; "She is a very controlling mother and
doesn't let her children grow up"; "The teacher knew how to keep the class in line"; "she keeps in
line")
5. control, verify -- (check or regulate (a scientific experiment) by conducting a parallel
experiment or comparing with another standard; "Are you controlling for the temperature?")
6. control -- (verify by using a duplicate register for comparison; "control an account")
7. see, check, insure, see to it, ensure, control, ascertain, assure -- (be careful or certain to do
something; make certain of something; "He verified that the valves were closed"; "See that the
curtains are closed"; "control the quality of the product")
8. master, control -- (have a firm understanding or knowledge of; be on top of; "Do you control
these data?")
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