Journal article

Inhibition of retinoblastoma protein degradation by interaction with the serpin plasminogen activator inhibitor 2 via a novel consensus motif

GA Darnell, TM Antalis, RW Johnstone, BW Stringer, SM Ogbourne, D Harrich, A Suhrbier

Molecular and Cellular Biology | AMER SOC MICROBIOLOGY | Published : 2003

Abstract

Plasminogen activator inhibitor-2 (PAI-2) is well documented as an inhibitor of the extracellular serine proteinase urokinase-type plasminogen activator (uPA) and is expressed in activated monocytes and macrophages, differentiating keratinocytes, and many tumors. Here we show that PAI-2 has a novel intracellular function as a retinoblastoma protein (Rb)-binding protein. PAI-2 colocalized with Rb in the nucleus and inhibited the turnover of Rb, which led to increases in Rb protein levels and Rb-mediated activities. Although PAI-2 contains an LXCXE motif, Rb binding was primarily mediated by the C-D interhelical region of PAI-2, which was found to bind to the C pocket of Rb. The C-D interhelic..

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