Chronic inflammation promotes retinoblastoma protein hyperphosphorylation and E2F1 activation.
Chronic inflammation contributes to tumorigenesis. The retinoblastoma protein (pRb), in its hyperphosphorylated form, releases E2 promoter binding factor-1 (E2F1), which drives cell proliferation. Here, we show that pRb is hyperphosphorylated in both mouse and human colitis. In turn, pRb hyperphosphorylation is associated with release of E2F1 from pRb, resulting in the activation of E2F1 target molecules involved in proliferation and apoptosis. These observations provide insight into the in vivo mechanisms associated with chronic colon inflammation and increased colon cancer risk.
Ying
Lei
L
Laboratory of Inflammatory-Driven Carcinogenesis, Department of Basic Pharmaceutical Sciences, South Carolina College of Pharmacy.
Marino
Jillian
J
Hussain
S Perwez
SP
Khan
Mohammed A
MA
You
Shaojin
S
Hofseth
Anne B
AB
Trivers
Glennwood E
GE
Dixon
Dan A
DA
Harris
Curtis C
CC
Hofseth
Lorne J
LJ
D000818:Animals; D048708:Cell Growth Processes / Q000502:physiology; D003093:Colitis, Ulcerative / Q000378:metabolism* / Q000473:pathology; D050687:E2F1 Transcription Factor / Q000378:metabolism*; D005786:Gene Expression Regulation; D006801:Humans; D007249:Inflammation / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D010766:Phosphorylation; D016160:Retinoblastoma Protein / Q000378:metabolism*
D050687:E2F1 Transcription Factor; D016160:Retinoblastoma Protein