The Biological Effects of C/EBPa in K562 Cells Depend on the Potency of the N-terminal Regulatory Region, Not on Specificity of the DNA Binding Domain
The transcription factor C/EBPa is more potent than C/EBPb in inducing granulocitic differentiation and inhibiting BCR/ABL-expressing cells. We took a "domain swapping" approach to assess biological effects, modulation of gene expression, and binding to C/EBPa-regulated promoters by wild-t...
Saved in:
Published in | The Journal of biological chemistry Vol. 285; no. 40; pp. 30837 - 30850 |
---|---|
Main Authors | , , , , , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
01.10.2010
|
Online Access | Get full text |
Cover
Loading…
Abstract | The transcription factor C/EBPa is more potent than C/EBPb in inducing granulocitic differentiation and inhibiting BCR/ABL-expressing cells. We took a "domain swapping" approach to assess biological effects, modulation of gene expression, and binding to C/EBPa-regulated promoters by wild-type and chimeric C/EBPa/C/EBPb proteins. Wild-type and N-C/EBPa+ C/EBPb-DBD induced transcription of the granulocyte-colony stimulating factor receptor (G-CSFR) gene, promoted differentiation, and suppressed proliferation of K562 cells vigorously; instead, wild-type C/EBPb and N-C/EBPb+C/EBPa-DBD had modest effects, although they bound the G-CSFR promoter like wild-type C/EBPa and N-C/EBPa+C/EBPb-DBD. Chimeric proteins consisting of the TAD of VP16 and the DBD of C/EBPa or C/EBPb inhibited proliferation and induced differentiation of K562 cells as effectively as wild-type C/EBPa. Gene expression profiles induced by C/EBPa resembled those modulated by N-C/EBPa+C/EBPb-DBD, whereas C/EBPb induced a pattern similar to that of N-C/EBPb+C/EBPa-DBD. C/EBPa activation induced changes in the expression of more cell cycle- and apoptosis-related genes than the other proteins and enhanced Imatinib-induced apoptosis of K562 cells. Expression of FOXO3a, a novel C/EBPa-regulated gene, was required for apoptosis but not for differentiation induction or proliferation inhibition of K562 cells. |
---|---|
AbstractList | The transcription factor C/EBPa is more potent than C/EBPb in inducing granulocitic differentiation and inhibiting BCR/ABL-expressing cells. We took a "domain swapping" approach to assess biological effects, modulation of gene expression, and binding to C/EBPa-regulated promoters by wild-type and chimeric C/EBPa/C/EBPb proteins. Wild-type and N-C/EBPa+ C/EBPb-DBD induced transcription of the granulocyte-colony stimulating factor receptor (G-CSFR) gene, promoted differentiation, and suppressed proliferation of K562 cells vigorously; instead, wild-type C/EBPb and N-C/EBPb+C/EBPa-DBD had modest effects, although they bound the G-CSFR promoter like wild-type C/EBPa and N-C/EBPa+C/EBPb-DBD. Chimeric proteins consisting of the TAD of VP16 and the DBD of C/EBPa or C/EBPb inhibited proliferation and induced differentiation of K562 cells as effectively as wild-type C/EBPa. Gene expression profiles induced by C/EBPa resembled those modulated by N-C/EBPa+C/EBPb-DBD, whereas C/EBPb induced a pattern similar to that of N-C/EBPb+C/EBPa-DBD. C/EBPa activation induced changes in the expression of more cell cycle- and apoptosis-related genes than the other proteins and enhanced Imatinib-induced apoptosis of K562 cells. Expression of FOXO3a, a novel C/EBPa-regulated gene, was required for apoptosis but not for differentiation induction or proliferation inhibition of K562 cells. The transcription factor C/EBPa is more potent than C/EBPb in inducing granulocitic differentiation and inhibiting BCR/ABL-expressing cells. We took a 'domain swappinga approach to assess biological effects, modulation of gene expression, and binding to C/EBPa-regulated promoters by wild-type and chimeric C/EBPa/C/EBPb proteins. Wild-type and N-C/EBPa+ C/EBPb-DBD induced transcription of the granulocyte-colony stimulating factor receptor (G-CSFR) gene, promoted differentiation, and suppressed proliferation of K562 cells vigorously; instead, wild-type C/EBPb and N-C/EBPb+C/EBPa-DBD had modest effects, although they bound the G-CSFR promoter like wild-type C/EBPa and N-C/EBPa+C/EBPb-DBD. Chimeric proteins consisting of the TAD of VP16 and the DBD of C/EBPa or C/EBPb inhibited proliferation and induced differentiation of K562 cells as effectively as wild-type C/EBPa. Gene expression profiles induced by C/EBPa resembled those modulated by N-C/EBPa+C/EBPb-DBD, whereas C/EBPb induced a pattern similar to that of N-C/EBPb+C/EBPa-DBD. C/EBPa activation induced changes in the expression of more cell cycle- and apoptosis-related genes than the other proteins and enhanced Imatinib-induced apoptosis of K562 cells. Expression of FOXO3a, a novel C/EBPa-regulated gene, was required for apoptosis but not for differentiation induction or proliferation inhibition of K562 cells. |
Author | Calabretta, Bruno Novi, Chiara Pecorari, Luisa Manzotti, Gloria Martinez, Robert V Guerzoni, Clara Lam, Eric W-F Corradini, Francesca Cattelani, Sara Fragliasso, Valentina Ferrari-Amorotti, Giovanna Soliera, Angela Rachele Zhang, Ying Mariani, Samanta Antonella |
Author_xml | – sequence: 1 givenname: Giovanna surname: Ferrari-Amorotti fullname: Ferrari-Amorotti, Giovanna – sequence: 2 givenname: Samanta surname: Mariani middlename: Antonella fullname: Mariani, Samanta Antonella – sequence: 3 givenname: Chiara surname: Novi fullname: Novi, Chiara – sequence: 4 givenname: Sara surname: Cattelani fullname: Cattelani, Sara – sequence: 5 givenname: Luisa surname: Pecorari fullname: Pecorari, Luisa – sequence: 6 givenname: Francesca surname: Corradini fullname: Corradini, Francesca – sequence: 7 givenname: Angela surname: Soliera middlename: Rachele fullname: Soliera, Angela Rachele – sequence: 8 givenname: Gloria surname: Manzotti fullname: Manzotti, Gloria – sequence: 9 givenname: Valentina surname: Fragliasso fullname: Fragliasso, Valentina – sequence: 10 givenname: Ying surname: Zhang fullname: Zhang, Ying – sequence: 11 givenname: Robert surname: Martinez middlename: V fullname: Martinez, Robert V – sequence: 12 givenname: Eric surname: Lam middlename: W-F fullname: Lam, Eric W-F – sequence: 13 givenname: Clara surname: Guerzoni fullname: Guerzoni, Clara – sequence: 14 givenname: Bruno surname: Calabretta fullname: Calabretta, Bruno |
BookMark | eNqFUE1PAjEQ7QETAT177c2LC23pdrdHvvyIiES5k9JOsWRpV1oO_BF_r7vReHUuMy_z3sub6aGODx4QuqFkQEnBh_utHrzQFrGSFayDuoQwmkmWl5eoF-OeNMUl7aKv9QfgiQtV2DmtKjy3FnSKOFg8Hc4nK4Wdx8-5YHgKVRXxDGrwBgePUyNchQRen1t2C5dZguPB-cbnDXanSqVwPLejC_4OL0Nqde81aGeddulPN1uOmwzeOL_Ds3BQzl-hC6uqCNe_vY_W9_P19DFbvD48TceLrBacZtwqkNIwQyznUkurjBBallQawqkilmglCkGtFc2O28JQZbZMS03A5FyN-uj2x7Y-hs8TxLQ5uKibQ5WHcIqbciQLQmRO_2UWgjWPLgsy-gaUXHdC |
ContentType | Journal Article |
DBID | 7TM |
DOI | 10.1074/jbc.M110.128272 |
DatabaseName | Nucleic Acids Abstracts |
DatabaseTitle | Nucleic Acids Abstracts |
DatabaseTitleList | Nucleic Acids Abstracts Nucleic Acids Abstracts |
DeliveryMethod | fulltext_linktorsrc |
Discipline | Anatomy & Physiology Chemistry |
EndPage | 30850 |
GroupedDBID | --- -DZ -ET -~X 0R~ 0SF 18M 29J 2WC 34G 39C 4.4 53G 5BI 5GY 5RE 5VS 79B 7TM 85S AAEDW AAFWJ AARDX AAXUO ABDNZ ABOCM ABPPZ ABRJW ACGFO ACNCT ADBBV ADIYS ADNWM ADVLN AENEX AEXQZ AFFNX AFOSN AFPKN AITUG AKRWK ALMA_UNASSIGNED_HOLDINGS AMRAJ AOIJS BAWUL BTFSW C1A CJ0 CS3 DIK DU5 E3Z EBS EJD F5P FDB FRP GROUPED_DOAJ GX1 H13 HH5 HYE IH2 KQ8 L7B N9A OK1 P-O P0W P2P R.V RHF RHI RNS ROL RPM SJN TBC TN5 TR2 UHB UKR UPT VQA W8F WH7 WOQ XSW YQT YSK YWH YZZ ZE2 ~02 ~KM |
ID | FETCH-LOGICAL-p641-4fae99d2d0f449c9fad66c9819d041a0f0ca6761ff69fa4f7d1adb2c9c0ed54a3 |
ISSN | 0021-9258 |
IngestDate | Fri Aug 16 02:01:21 EDT 2024 Fri Aug 16 20:43:44 EDT 2024 |
IsPeerReviewed | true |
IsScholarly | true |
Issue | 40 |
Language | English |
LinkModel | OpenURL |
MergedId | FETCHMERGED-LOGICAL-p641-4fae99d2d0f449c9fad66c9819d041a0f0ca6761ff69fa4f7d1adb2c9c0ed54a3 |
Notes | ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-1 content type line 23 |
PQID | 762272870 |
PQPubID | 23462 |
PageCount | 14 |
ParticipantIDs | proquest_miscellaneous_839700951 proquest_miscellaneous_762272870 |
PublicationCentury | 2000 |
PublicationDate | 20101001 |
PublicationDateYYYYMMDD | 2010-10-01 |
PublicationDate_xml | – month: 10 year: 2010 text: 20101001 day: 01 |
PublicationDecade | 2010 |
PublicationTitle | The Journal of biological chemistry |
PublicationYear | 2010 |
SSID | ssj0000491 |
Score | 2.0222905 |
Snippet | The transcription factor C/EBPa is more potent than C/EBPb in inducing granulocitic differentiation and inhibiting BCR/ABL-expressing cells. We took a "domain... The transcription factor C/EBPa is more potent than C/EBPb in inducing granulocitic differentiation and inhibiting BCR/ABL-expressing cells. We took a 'domain... |
SourceID | proquest |
SourceType | Aggregation Database |
StartPage | 30837 |
Title | The Biological Effects of C/EBPa in K562 Cells Depend on the Potency of the N-terminal Regulatory Region, Not on Specificity of the DNA Binding Domain |
URI | https://search.proquest.com/docview/762272870 https://search.proquest.com/docview/839700951 |
Volume | 285 |
hasFullText | 1 |
inHoldings | 1 |
isFullTextHit | |
isPrint | |
link | http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwnV1bb9MwFLbKeIAXBBuIMUDnAfFSsjWpm9SPJeuY2BqGyKS-VY6TSEVtgrp0EvwQfgy_jnNs5wIMcXmJcrEjy-eTz7H9-TuMvUCvhl4nJaZaKh3ujoWT5CJxRJpw9LYiDXQeslnkn17yt_PRvNf71mEtbavkUH258VzJ_1gV36Fd6ZTsP1i2-Sm-wHu0L17Rwnj9axubZJK6q6ctNyPEn05fX0hazjjD4KMfZqvVFY4ulPLWbhD0L8pKH7y0NIHIscwYktvXGepp_x1vl_ZQVllRTZ2xnnQnqqbmcTTBdpjzMcflWlo1749tKztxb9I2WNXZ5jqr2jR5dybrclNWhmnwhuiyRdG4jxkWMImo-h_kGoEhSQGhJLpOUyYqr5eGTLCUm5aLRFqiq6au_WCXPIg-MqiXPOojCK4jPKP5Xg_jnkn9Y_FqNKDsqDzEODPouPgh6fTd6D8woCL_kajDmaulN8aeySz0o1J39G5xcnl-voin8_gWu-0FYkR00rP3rVI9zrxMtkbb1FpWKuBHP_3-lyhAhzbxfXbP2gYmBmAPWC8rdtnepEAArD_DS9AsYb39ssvuhLXN9thXtCy0-AOLPyhzCI8IfbAsgNAHGn1g0AdlAQgasOij0vTYog9a9IFB3ytA7FG9Dvbqeog9sNgDg72HLD6ZxuGpY_N8OJ987jo8l5kQKQ4YOedCiVymvq8EhqrpgLtykA-U9APfzXMfv_E8SF2ZJp4SapClIy6Hj9hOgSh7zCAgdT6VCS9QHvfHrsQOxkf0UZkaBsrdZ1B39QL7ivbGZJGV26sFxgRoCnRevy-CU4lAz0ie_LnIAbvbAvcp26k22-wZRq9V8lzD5DsEA5zn |
link.rule.ids | 315,786,790,27955,27956 |
linkProvider | Colorado Alliance of Research Libraries |
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=The+Biological+Effects+of+C%2FEBPa+in+K562+Cells+Depend+on+the+Potency+of+the+N-terminal+Regulatory+Region%2C+Not+on+Specificity+of+the+DNA+Binding+Domain&rft.jtitle=The+Journal+of+biological+chemistry&rft.au=Ferrari-Amorotti%2C+Giovanna&rft.au=Mariani%2C+Samanta+Antonella&rft.au=Novi%2C+Chiara&rft.au=Cattelani%2C+Sara&rft.date=2010-10-01&rft.issn=0021-9258&rft.volume=285&rft.issue=40&rft.spage=30837&rft.epage=30850&rft_id=info:doi/10.1074%2Fjbc.M110.128272&rft.externalDBID=NO_FULL_TEXT |
thumbnail_l | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/lc.gif&issn=0021-9258&client=summon |
thumbnail_m | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/mc.gif&issn=0021-9258&client=summon |
thumbnail_s | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/sc.gif&issn=0021-9258&client=summon |