New perspectives on retinoblastoma family functions in differentiation.
Cell differentiation is a coordinated process that includes cell cycle exit and the expression of unique genes to specify tissue identity. The focus of this review is the recent progress in understanding the functions of the RB family (RB, p130,p107) in cell differentiation. Much work has focused on the functions of RB in G1 regulation. However, much evidence now suggests a diverse function in differentiation. For discussion, differentiation will be divided into three general steps: cell cycle exit, apoptosis protection, and tissue-specific gene expression. These processes are coordinated to provide the final and unique tissue characteristics. The RB family and targets such as E2F and HBP1 have functions in each step. While there is much knowledge on each separate step of differentiation, the mechanisms that coordinate cell cycle and tissue-specific events are still not known. New evidence suggests that this coordination contains both positive and negative regulation of tissue-specific gene expression. RB. p130, HBP1, and other proteins appear to have unexpected functions in regulating tissue-specific gene expression. The ubiquitous expressions of these proteins suggest membership in a new and general pathway to coordinate cell cycle events with tissue-specific gene expression during differentiation. The collective observations hypothesize the existence of a differentiation checkpoint to insure fidelity.
Yee
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The Department of Biochemistry, Tufts University School of Medicine, 136 Harrison Ave., Boston, MA 02111, USA. ayee@opal.tufts.edu
Shih
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Tevosian
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D017667:Adipocytes / Q000166:cytology; D000818:Animals; D017209:Apoptosis; D002352:Carrier Proteins; D002453:Cell Cycle; D018797:Cell Cycle Proteins; D002454:Cell Differentiation; D002460:Cell Line; D004268:DNA-Binding Proteins; D050684:E2F Transcription Factors; D005786:Gene Expression Regulation; D006609:High Mobility Group Proteins / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D009132:Muscles / Q000166:cytology; D009687:Nuclear Proteins / Q000235:genetics / Q000502:physiology*; D009928:Organ Specificity; D010750:Phosphoproteins / Q000235:genetics / Q000502:physiology*; D011506:Proteins; D012097:Repressor Proteins / Q000502:physiology; D016160:Retinoblastoma Protein / Q000235:genetics / Q000502:physiology*; D056465:Retinoblastoma-Binding Protein 1; D050720:Retinoblastoma-Like Protein p107; D050717:Retinoblastoma-Like Protein p130; D050680:Transcription Factor DP1; D014157:Transcription Factors / Q000502:physiology
C533431:Arid4a protein, mouse; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D050684:E2F Transcription Factors; C486328:HBP1 protein, human; C486329:Hbp1 protein, mouse; D006609:High Mobility Group Proteins; D009687:Nuclear Proteins; D010750:Phosphoproteins; D011506:Proteins; C489485:Rbl1 protein, mouse; C493838:Rbl2 protein, mouse; D012097:Repressor Proteins; D016160:Retinoblastoma Protein; D056465:Retinoblastoma-Binding Protein 1; D050720:Retinoblastoma-Like Protein p107; D050717:Retinoblastoma-Like Protein p130; D050680:Transcription Factor DP1; D014157:Transcription Factors