Control of Cell Proliferation by Progress in Differentiation: Clues to Mechanisms of Aging, Cancer Causation and Therapy
In multicellular organisms, the control of cell proliferation occurs, in part, by modulating the progress in differentiation. In normal and neoplastic cells, for example, progress towards terminal differentiation concludes cell proliferation, whereas arrest of progress in differentiation causes unco...
Saved in:
Published in | Journal of theoretical biology Vol. 193; no. 4; pp. 663 - 678 |
---|---|
Main Authors | , |
Format | Journal Article |
Language | English |
Published |
England
Elsevier Ltd
21.08.1998
|
Subjects | |
Online Access | Get full text |
Cover
Loading…
Abstract | In multicellular organisms, the control of cell proliferation occurs, in part, by modulating the progress in differentiation. In normal and neoplastic cells, for example, progress towards terminal differentiation concludes cell proliferation, whereas arrest of progress in differentiation causes uncontrolled cell proliferation. Evidence is presented according to which the progress in differentiation depends on an increase in the ratio between mitochondrial differentiation promoting activity and nuclear differentiation preventing activity. This ratio is low in embryonic cells and in stem cells, due to low mitochondrical content, but increases by a rate of mitochondrial multipliation that is larger than a doubling of mitochondrial content per cell cycle. The rate of mitochondrical multiplication, thus, decides on the progress in differentiation and controls the number of amplification divisions between cell determination and terminal differentiation. This rate is modifiable by extracellular signals and cellular defects. Mutations for example in nuclear genes coding for mitochondrial proteins, are likely to decrease the rate so much that differentiation is arrested with ensuing neoplastic growth. Agents used in differentiation therapy and ionizing radiation overcome this arrest: the cell cycle is sensitive to these agents, but not the mitochondria which multiply during the transitory cell cycle inhibition, thus increasing the differentiation promoting activity. Differentiation arrest can be circumvented also by direct inhibition of nuclear differentiation preventing activity at the level of transcription or translation, whereas corresponding inhibition of mitochondrial differentiation promoting activity prevents differentiation. Accumulation of non-specific genetic damage causes persisting cell cycle prolongation and enhancement of differentiation which, apparently, are involved in senescence. The recent finding of increase in mitochondrial mass prior to release of cytochrome c, induction of differentiation and apoptosis points to similarities in the initial molecular pathways of differentiation and apoptosis. |
---|---|
AbstractList | In multicellular organisms, the control of cell proliferation occurs, in part, by modulating the progress in differentiation. In normal and neoplastic cells, for example, progress towards terminal differentiation concludes cell proliferation, whereas arrest of progress in differentiation causes uncontrolled cell proliferation. Evidence is presented according to which the progress in differentiation depends on an increase in the ratio between mitochondrial differentiation promoting activity and nuclear differentiation preventing activity. This ratio is low in embryonic cells and in stem cells, due to low mitochondrial content, but increases by a rate of mitochondrial multiplication that is larger than a doubling of mitochondrial content per cell cycle. The rate of mitochondrial multiplication, thus, decides on the progress in differentiation and controls the number of amplification divisions between cell determination and terminal differentiation. This rate is modifiable by extracellular signals and cellular defects. Mutations, for example in nuclear genes coding for mitochondrial proteins, are likely to decrease the rate so much that differentiation is arrested with ensuing neoplastic growth. Agents used in differentiation therapy and ionizing radiation overcome this arrest: the cell cycle is sensitive to these agents, but not the mitochondria which multiply during the transitory cell cycle inhibition, thus increasing the differentiation promoting activity. Differentiation arrest can be circumvented also by direct inhibition of nuclear differentiation preventing activity at the level of transcription or translation, whereas corresponding inhibition of mitochondrial differentiation promoting activity prevents differentiation. Accumulation of non-specific genetic damage causes persisting cell cycle prolongation and enhancement of differentiation which, apparently, are involved in senescence. The recent finding of increase in mitochondrial mass prior to release of cytochrome c, induction of differentiation, and apoptosis points to similarities in the initial molecular pathways of differentiation and apoptosis. In multicellular organisms, the control of cell proliferation occurs, in part, by modulating the progress in differentiation. In normal and neoplastic cells, for example, progress towards terminal differentiation concludes cell proliferation, whereas arrest of progress in differentiation causes uncontrolled cell proliferation. Evidence is presented according to which the progress in differentiation depends on an increase in the ratio between mitochondrial differentiation promoting activity and nuclear differentiation preventing activity. This ratio is low in embryonic cells and in stem cells, due to low mitochondrical content, but increases by a rate of mitochondrial multipliation that is larger than a doubling of mitochondrial content per cell cycle. The rate of mitochondrical multiplication, thus, decides on the progress in differentiation and controls the number of amplification divisions between cell determination and terminal differentiation. This rate is modifiable by extracellular signals and cellular defects. Mutations for example in nuclear genes coding for mitochondrial proteins, are likely to decrease the rate so much that differentiation is arrested with ensuing neoplastic growth. Agents used in differentiation therapy and ionizing radiation overcome this arrest: the cell cycle is sensitive to these agents, but not the mitochondria which multiply during the transitory cell cycle inhibition, thus increasing the differentiation promoting activity. Differentiation arrest can be circumvented also by direct inhibition of nuclear differentiation preventing activity at the level of transcription or translation, whereas corresponding inhibition of mitochondrial differentiation promoting activity prevents differentiation. Accumulation of non-specific genetic damage causes persisting cell cycle prolongation and enhancement of differentiation which, apparently, are involved in senescence. The recent finding of increase in mitochondrial mass prior to release of cytochrome c, induction of differentiation and apoptosis points to similarities in the initial molecular pathways of differentiation and apoptosis. |
Author | Peterson, Hans-Peter von Wagenheim, Karl-Hartmut |
Author_xml | – sequence: 1 givenname: Karl-Hartmut surname: von Wagenheim fullname: von Wagenheim, Karl-Hartmut – sequence: 2 givenname: Hans-Peter surname: Peterson fullname: Peterson, Hans-Peter |
BackLink | https://www.ncbi.nlm.nih.gov/pubmed/9745759$$D View this record in MEDLINE/PubMed |
BookMark | eNqFkc1v1DAQxS3UqmwLV25IPnEi23EcxzG3KuWjUis4lLPlOOOtq6y92FnE_vc47Iob4jQav-efZuZdkrMQAxLyhsGaAbTXz_Pg10ypbg2SsxdkxUCJqhMNOyMrgLquBFP8JbnM-RkAVMPbC3KhZCOkUCvyq49hTnGi0dEep4l-K413mMzsY6DDYXnYJMyZ-kBvvSsShtn_kT_QftpjpnOkD2ifTPB5mxfSzcaHzXvam2AxlbLPR5wJI318KvDd4RU5d2bK-PpUr8j3Tx8f-y_V_dfPd_3NfWXLpHM1Ng3U3CgmoRPS1DUXzrqySNsoCYZZ3iIfuBRWtR1IOXTgBDdWSumaoav5FXl35O5S_FGGnfXWZ1s2NQHjPmvJFYCA5r9GJplQrVqI66PRpphzQqd3yW9NOmgGeslEL5noJRO9ZFI-vD2R98MWx7_2UwhF7446ljv89Jh0th7L6Uaf0M56jP5f6N_c5Jwi |
CitedBy_id | crossref_primary_10_1016_j_bbamcr_2007_10_001 crossref_primary_10_1269_jrr_11099 crossref_primary_10_1186_s12858_015_0044_7 crossref_primary_10_1007_s00259_008_1024_6 crossref_primary_10_1002_jcp_21392 crossref_primary_10_1016_j_pharmthera_2008_11_002 crossref_primary_10_1152_ajpheart_00700_2002 crossref_primary_10_1016_S1040_8428_02_00121_X crossref_primary_10_1089_ars_2009_2513 crossref_primary_10_1089_rej_1_1998_1_375 crossref_primary_10_1016_j_ejphar_2019_04_048 crossref_primary_10_1290_1071_2690_2002_038_0123_MIECIP_2_0_CO_2 crossref_primary_10_1006_excr_2000_4810 crossref_primary_10_1111_bph_12253 crossref_primary_10_1186_1742_4682_5_23 crossref_primary_10_1038_s41419_022_04736_6 crossref_primary_10_1007_s00418_011_0786_2 crossref_primary_10_1016_j_mehy_2006_10_055 crossref_primary_10_1111_j_0014_3820_2003_tb00306_x crossref_primary_10_1016_S0378_5122_00_00190_0 crossref_primary_10_1002_bit_20936 crossref_primary_10_1007_s10522_008_9209_8 crossref_primary_10_3168_jds_S0022_0302_03_73880_6 crossref_primary_10_1002_advs_202307554 crossref_primary_10_1016_j_diff_2008_12_004 crossref_primary_10_1016_j_jphotochem_2012_11_010 crossref_primary_10_1139_w00_096 crossref_primary_10_7554_eLife_49683 crossref_primary_10_1016_j_gene_2005_03_020 crossref_primary_10_1007_s00432_008_0381_7 crossref_primary_10_1554_0014_3820_2003_057_0939_PMSASA_2_0_CO_2 crossref_primary_10_1667_RR2725_1 crossref_primary_10_1002_adhm_201500441 crossref_primary_10_1016_j_ydbio_2004_03_014 crossref_primary_10_1038_sj_bjc_6603868 crossref_primary_10_1093_jrr_rrs125 crossref_primary_10_1242_jcs_114_5_1011 crossref_primary_10_1371_journal_pone_0124833 crossref_primary_10_1006_jtbi_2001_2342 crossref_primary_10_1016_j_mrfmmm_2007_06_002 crossref_primary_10_1073_pnas_0603363103 crossref_primary_10_1177_107327480701400104 crossref_primary_10_1371_journal_pcbi_0030250 crossref_primary_10_1002__SICI_1097_0215_19991029_83_3_359__AID_IJC11_3_0_CO_2_6 crossref_primary_10_1006_jsbi_1999_4147 crossref_primary_10_1016_j_nano_2007_08_004 crossref_primary_10_1016_S0378_1119_00_00582_5 crossref_primary_10_1038_sj_bjc_6600959 |
ContentType | Journal Article |
Copyright | 1998 Academic Press |
Copyright_xml | – notice: 1998 Academic Press |
DBID | CGR CUY CVF ECM EIF NPM AAYXX CITATION 8FD FR3 P64 RC3 7X8 |
DOI | 10.1006/jtbi.1998.0731 |
DatabaseName | Medline MEDLINE MEDLINE (Ovid) MEDLINE MEDLINE PubMed CrossRef Technology Research Database Engineering Research Database Biotechnology and BioEngineering Abstracts Genetics Abstracts MEDLINE - Academic |
DatabaseTitle | MEDLINE Medline Complete MEDLINE with Full Text PubMed MEDLINE (Ovid) CrossRef Genetics Abstracts Engineering Research Database Technology Research Database Biotechnology and BioEngineering Abstracts MEDLINE - Academic |
DatabaseTitleList | MEDLINE Genetics Abstracts MEDLINE - Academic |
Database_xml | – sequence: 1 dbid: NPM name: PubMed url: https://proxy.k.utb.cz/login?url=http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed sourceTypes: Index Database – sequence: 2 dbid: EIF name: MEDLINE url: https://proxy.k.utb.cz/login?url=https://www.webofscience.com/wos/medline/basic-search sourceTypes: Index Database |
DeliveryMethod | fulltext_linktorsrc |
Discipline | Biology |
EISSN | 1095-8541 |
EndPage | 678 |
ExternalDocumentID | 10_1006_jtbi_1998_0731 9745759 S0022519398907317 |
Genre | Journal Article Review |
GroupedDBID | --- --K --M -DZ -~X .GJ .~1 1B1 1RT 1~. 1~5 29L 3O- 4.4 457 4G. 53G 5GY 5RE 5VS 7-5 71M 8P~ 9JM AABNK AABVA AACTN AAEDT AAEDW AAIAV AAIKJ AAKOC AALCJ AALRI AAOAW AAQFI AAQXK AATLK AAXUO ABFRF ABJNI ABMAC ABTAH ABYKQ ACDAQ ACGFO ACGFS ACNCT ACRLP ADBBV ADEZE ADFGL ADMUD ADQTV AEFWE AEKER AENEX AEQOU AFFNX AFKWA AFTJW AFXIZ AGHFR AGUBO AGYEJ AHHHB AI. AIEXJ AIKHN AITUG AJBFU AJOXV ALMA_UNASSIGNED_HOLDINGS AMFUW AMRAJ ASPBG AVWKF AXJTR AZFZN BKOJK BLXMC CAG CBWCG COF CS3 DM4 DU5 EBS EFBJH EFLBG EJD EO8 EO9 EP2 EP3 F5P FDB FEDTE FGOYB FIRID FNPLU FYGXN G-Q HLV HVGLF IHE J1W KOM LG5 LW8 M41 MO0 N9A O-L OAUVE OZT P-9 P2P PC. Q38 R2- ROL RPZ SAB SCC SDF SDG SDP SES SPCBC SSA SSZ T5K TN5 VH1 XPP YQT ZMT ZU3 ZY4 ~02 ~G- ~KM AAXKI AKRWK CGR CUY CVF ECM EIF NPM 0R~ AAYXX ABFNM ABGRD ABXDB AEBSH AFJKZ CITATION FA8 G-2 GBLVA HZ~ H~9 MVM O9- OHT P-8 RIG RNS SEW UQL WUQ ZGI ZXP 8FD FR3 P64 RC3 7X8 |
ID | FETCH-LOGICAL-c436t-d44023a9170857a2235fcf00064970a1c36e3b375c968077b80f53ac777f4b823 |
IEDL.DBID | .~1 |
ISSN | 0022-5193 |
IngestDate | Fri Aug 16 22:04:13 EDT 2024 Fri Aug 16 21:36:57 EDT 2024 Thu Sep 26 16:24:45 EDT 2024 Sat Sep 28 08:36:58 EDT 2024 Fri Feb 23 02:22:46 EST 2024 |
IsPeerReviewed | true |
IsScholarly | true |
Issue | 4 |
Language | English |
LinkModel | DirectLink |
MergedId | FETCHMERGED-LOGICAL-c436t-d44023a9170857a2235fcf00064970a1c36e3b375c968077b80f53ac777f4b823 |
Notes | ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-1 content type line 23 ObjectType-Feature-3 ObjectType-Review-1 |
PMID | 9745759 |
PQID | 17159692 |
PQPubID | 23462 |
PageCount | 16 |
ParticipantIDs | proquest_miscellaneous_73900504 proquest_miscellaneous_17159692 crossref_primary_10_1006_jtbi_1998_0731 pubmed_primary_9745759 elsevier_sciencedirect_doi_10_1006_jtbi_1998_0731 |
PublicationCentury | 1900 |
PublicationDate | 1998-08-21 |
PublicationDateYYYYMMDD | 1998-08-21 |
PublicationDate_xml | – month: 08 year: 1998 text: 1998-08-21 day: 21 |
PublicationDecade | 1990 |
PublicationPlace | England |
PublicationPlace_xml | – name: England |
PublicationTitle | Journal of theoretical biology |
PublicationTitleAlternate | J Theor Biol |
PublicationYear | 1998 |
Publisher | Elsevier Ltd |
Publisher_xml | – name: Elsevier Ltd |
SSID | ssj0009436 |
Score | 1.8307699 |
SecondaryResourceType | review_article |
Snippet | In multicellular organisms, the control of cell proliferation occurs, in part, by modulating the progress in differentiation. In normal and neoplastic cells,... |
SourceID | proquest crossref pubmed elsevier |
SourceType | Aggregation Database Index Database Publisher |
StartPage | 663 |
SubjectTerms | Aging - pathology Animals Cell Differentiation - drug effects Cell Differentiation - physiology Cell Differentiation - radiation effects Cell Division - physiology Cell Nucleus - physiology Cell Transformation, Neoplastic - pathology Cellular Senescence - physiology Humans Mitochondria - physiology Neoplasms - therapy |
Title | Control of Cell Proliferation by Progress in Differentiation: Clues to Mechanisms of Aging, Cancer Causation and Therapy |
URI | https://dx.doi.org/10.1006/jtbi.1998.0731 https://www.ncbi.nlm.nih.gov/pubmed/9745759 https://search.proquest.com/docview/17159692 https://search.proquest.com/docview/73900504 |
Volume | 193 |
hasFullText | 1 |
inHoldings | 1 |
isFullTextHit | |
isPrint | |
link | http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwnV1LS8QwEA6iCF7EJ67PHAQvdnfbpEnrbanKquziQWFvIWkbqKxdcbugF3-7M02reNiLp0Jo2vDNdB50vhlCzq1vLUTGxrM6jjzOpfFMGFkPPBELjAgli5GNPBqL4TO_n4STFZK0XBgsq2xsv7PptbVuVnoNmr23okCOb4C0SxZHkOCBG0QGOzgj0Onu12-ZR8zrMYF11Tre3TZu7IveS2UKZOtFXdy_zDEtCzxrB3S7RTabyJEO3OG2yUpe7pB1N0vyc5d8JK7onM4sTfLplD7iPB6bOwlT84kLdXJNi5JeN3NRKieZK5pM4eW0mtFRjlzgYv46xycNcIbRJU1QN97hsnDFP1SXGX1yDQn2yPPtzVMy9JqxCl4KWFRexiFnZBryNOxur0EqoU1tHZzEsq_9lImcGSbDNBZRX0oT9W3IdCqltNxEAdsnq-WszA8INRH3AxMLmWWWC18by1NhjIa0x4RpJjvkosVUvbnuGcr1SRYK0VeIvkL0O8RvIVd_5K_AtC_dc9bKRsFHgX86dJnPFnPlS4jSRBwsvwN0EFvf8A7Zd0L9OR8kWDi09PAfBzoiG46yCMbHPyar1fsiP4GYpTKntVKekrXB3cNw_A1EP-sB |
link.rule.ids | 315,786,790,4521,24144,27957,27958,45620,45714 |
linkProvider | Elsevier |
linkToHtml | http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwnV1La9tAEB5Sh9JeStI21G2T7KGQS1Rb2tWu1JtREpyHTQ4O5LbsSlpQcOUQy9D8-85opYYefMlJILSr5ZvRPNB8MwA_XOgcRsY2cCZNAiGUDWycuAA9EY-sjBVPiY08m8vpnbi6j-93IOu5MFRW2dl-b9Nba93dGXVojh6riji-EdEueZpggodu8A3siliFYgC7k8vr6fyl965oJwW2heu0oO_dOJajh8ZWRNhLftIW23zTttiz9UEXe_ChCx7ZxJ9vH3bK-iO89eMknz_Bn8zXnbOVY1m5XLJbGsnjSi9kZp_pRptfs6pmZ91olMYL5xfLlvhy1qzYrCQ6cLX-vaadJjTG6JRlpB5PeNn4-h9m6oItfE-Cz3B3cb7IpkE3WSHIEYsmKASmjdxgqkYN7g0KJna5a-OTVI1NmHNZcstVnKcyGStlk7GLucmVUk7YJOIHMKhXdfkFmE1EGNlUqqJwQobGOpFLaw1mPjbOCzWEkx5T_egbaGjfKllqQl8T-prQH0LYQ67_UwGN1n3rmuNeNhq_C_rZYepytVnrUGGgJtNo-xOohtT9RgzhwAv13_kwx6K5pV9fcaBjeDddzG70zeX8-hu89wxGtEXhdxg0T5vyEEOYxh51KvoXY2Tttw |
openUrl | ctx_ver=Z39.88-2004&ctx_enc=info%3Aofi%2Fenc%3AUTF-8&rfr_id=info%3Asid%2Fsummon.serialssolutions.com&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Control+of+Cell+Proliferation+by+Progress+in+Differentiation%3A+Clues+to+Mechanisms+of+Aging%2C+Cancer+Causation+and+Therapy&rft.jtitle=Journal+of+theoretical+biology&rft.au=von+Wagenheim%2C+Karl-Hartmut&rft.au=Peterson%2C+Hans-Peter&rft.date=1998-08-21&rft.issn=0022-5193&rft.volume=193&rft.issue=4&rft.spage=663&rft.epage=678&rft_id=info:doi/10.1006%2Fjtbi.1998.0731&rft.externalDBID=n%2Fa&rft.externalDocID=10_1006_jtbi_1998_0731 |
thumbnail_l | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/lc.gif&issn=0022-5193&client=summon |
thumbnail_m | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/mc.gif&issn=0022-5193&client=summon |
thumbnail_s | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/sc.gif&issn=0022-5193&client=summon |