Table 1 Examples of Cellular Regulatory Proteins Degraded by the 26S Proteasome

p21^WAF1/Cip1

CKI, cell cycle regulation

Cell cycle progression; differentiation

Blagosklonny et al, 1996; Di Cunto et al, 1998

p27^Kip1

CKI, cell cycle regulation

Cell cycle progression;/enhanced degradation: tumor progression; inhibition of differentiation

Pagano et al, 1995; Sgambato et al, 2000; Baldassarre et al, 2000

p19^INK4d

CKI, cell cycle regulation

Cell cycle progression

Thullberg et al, 2000

Cyclin A

Cell cycle regulation

Completion of mitosis; entry into S-phase

Yew, 2001

Cyclin D

Cell cycle regulation

Completion of S-phase?/defective degradation in breast cancer

Diehl et al, 1997; Russel et al, 1999

Cyclin E

Cell cycle regulation

Entry into S-phase; progression through S-phase

Singer et al, 1999

E2F

Cell cycle regulation

Completion of G1-to-S transitions

Marti et al, 1999

Cdc6

Initiation of DNA replication

Completion of DNA replication in G1-phase

Peterson et al, 2000

Geminin

Inhibition of DNA replication

Entry into S-phase; completion of mitosis

McGarry and Kirschner, 1998

c-IAP1, XIAP

Inhibition of apoptosis

Promotion of apoptosis;/degradation after autoubiquitination in response to apoptotic stimuli

Yang et al, 2000; Suzuki et al, 2001

Bcl-2

Inhibition of apoptosis

Promotion of apoptosis

Dimmeler et al, 1999; Breitschopf et al, 2000a

IκBα

Inhibitor of NF-κB

Inhibition of apoptosis through activation of NF-κB

Palombella et al, 1994; Chen et al, 1995; Mayo et al, 1997

NF-κB precursor

Maturation of NF-κB

Maintenance of NF-κB abundance

Palombella et al, 1994; Lin et al, 1998

p53

Maintenance of genetic integrity; induction of apoptosis/cell cycle arrest

Posttranslational regulation of p53;/enhanced degradation: promotion of neoplastic proliferation

Maki et al, 1996; Masdehors et al, 2000; Hengstermann et al, 2001

Bax

Promotion of apoptosis

Inhibition of apoptosis;/increased degradation in prostate carcinomas

Chang et al, 1998; Li and Dou, 2000

Bid

Promotion of apoptosis

Inhibition of apoptosis

Breitschopf et al, 2000b

c-Myc

Promotion of proliferation

Inhibition of proliferation;/decreased degradation in lymphomas

Gregory and Hann, 2000

β-Catenin

Signal transduction

Regulation of differentiation?/decreased degradation in inherited colon carcinomas

Aberle et al, 1997; Korink et al, 1997; Morin et al, 1997

p57^Kip2

CKI, differentiation, cell cycle regulation

Inhibition of differentiation

Urano et al, 1999

Cdc25a

Inhibition of differentiation

Induction of differentiation; cell cycle regulation

Bernardi et al, 2000

CPEB

Translational activation

Completion of meiosis (oocyte maturation)

Reverte et al, 2001