Commentary: locating the restriction point
Abstract Attempts to map the Restriction Point in the mammalian cell cycle typically involve stimulating quiescent cells with mitogens for increasing intervals, removing the stimulus and then determining the proportion of cells that reach S phase at some point later. This “fixed point” estimate assu...
| Main Author: | |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2023-02-01
|
| Series: | Cell Division |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s13008-023-00085-8 |
| _version_ | 1811165785866895360 |
|---|---|
| author | Robert F. Brooks |
| author_facet | Robert F. Brooks |
| author_sort | Robert F. Brooks |
| collection | DOAJ |
| description | Abstract Attempts to map the Restriction Point in the mammalian cell cycle typically involve stimulating quiescent cells with mitogens for increasing intervals, removing the stimulus and then determining the proportion of cells that reach S phase at some point later. This “fixed point” estimate assumes that further cell cycle commitment ceases as soon as the stimulus is removed. In fact, kinetic analysis shows that the probability of cell cycle commitment does not fall back to its initial low value, immediately after a pulse of mitogens, but may instead remain slightly elevated for some while afterwards, compared to the starting quiescent population. Thus, cells entering S phase after a brief exposure to mitogens are not those that pass the Restriction Point early. Rather, they represent cells that continue on to S phase as a result of this residual, low probability of cell cycle commitment. Instead, the mitogen-regulated process(es) affecting the probability of cell cycle commitment are much closer to the start of S phase itself. Since the acquisition of (apparent) mitogen independence is such a poor indicator of the timing of cell cycle commitment, it is argued that a better measure is the point of insensitivity to CDK4,6 inhibitors such as palbociclib, which indicates when hyperphosphorylation of the Retinoblastoma Protein, RB, ceases to be dependent on mitogen-signalling pathways regulating CDK4,6/cyclin D activity. |
| first_indexed | 2024-04-10T15:42:48Z |
| format | Article |
| id | doaj.art-9d126629450c4f398c82f1d26d2d8a51 |
| institution | Directory Open Access Journal |
| issn | 1747-1028 |
| language | English |
| last_indexed | 2024-04-10T15:42:48Z |
| publishDate | 2023-02-01 |
| publisher | BMC |
| record_format | Article |
| series | Cell Division |
| spelling | doaj.art-9d126629450c4f398c82f1d26d2d8a512023-02-12T12:17:53ZengBMCCell Division1747-10282023-02-011811610.1186/s13008-023-00085-8Commentary: locating the restriction pointRobert F. Brooks0Molecular and Clinical Sciences Research Institute, St George’s University of LondonAbstract Attempts to map the Restriction Point in the mammalian cell cycle typically involve stimulating quiescent cells with mitogens for increasing intervals, removing the stimulus and then determining the proportion of cells that reach S phase at some point later. This “fixed point” estimate assumes that further cell cycle commitment ceases as soon as the stimulus is removed. In fact, kinetic analysis shows that the probability of cell cycle commitment does not fall back to its initial low value, immediately after a pulse of mitogens, but may instead remain slightly elevated for some while afterwards, compared to the starting quiescent population. Thus, cells entering S phase after a brief exposure to mitogens are not those that pass the Restriction Point early. Rather, they represent cells that continue on to S phase as a result of this residual, low probability of cell cycle commitment. Instead, the mitogen-regulated process(es) affecting the probability of cell cycle commitment are much closer to the start of S phase itself. Since the acquisition of (apparent) mitogen independence is such a poor indicator of the timing of cell cycle commitment, it is argued that a better measure is the point of insensitivity to CDK4,6 inhibitors such as palbociclib, which indicates when hyperphosphorylation of the Retinoblastoma Protein, RB, ceases to be dependent on mitogen-signalling pathways regulating CDK4,6/cyclin D activity.https://doi.org/10.1186/s13008-023-00085-8Restriction pointQuiescenceMitogen stimulationRetinoblastoma protein (RB)Cyclin-dependent kinases 4 and 6 (CDK4,6)Cyclin-dependent kinase 2 (CDK2) |
| spellingShingle | Robert F. Brooks Commentary: locating the restriction point Cell Division Restriction point Quiescence Mitogen stimulation Retinoblastoma protein (RB) Cyclin-dependent kinases 4 and 6 (CDK4,6) Cyclin-dependent kinase 2 (CDK2) |
| title | Commentary: locating the restriction point |
| title_full | Commentary: locating the restriction point |
| title_fullStr | Commentary: locating the restriction point |
| title_full_unstemmed | Commentary: locating the restriction point |
| title_short | Commentary: locating the restriction point |
| title_sort | commentary locating the restriction point |
| topic | Restriction point Quiescence Mitogen stimulation Retinoblastoma protein (RB) Cyclin-dependent kinases 4 and 6 (CDK4,6) Cyclin-dependent kinase 2 (CDK2) |
| url | https://doi.org/10.1186/s13008-023-00085-8 |
| work_keys_str_mv | AT robertfbrooks commentarylocatingtherestrictionpoint |