p107 uses a p21CIP1-related domain to bind cyclin/cdk2 and regulate interactions with E2F.

Zhu, Liang; Harlow, Ed; Dynlacht, Brian David

doi:10.1101/gad.9.14.1740

Cited by 249 publications

(237 citation statements)

References 44 publications

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“…P21 has been shown to compete with both p107 and p130 for interactions with cyclin A/ cdk2 and cyclin E/cdk2 (Zhu et al, 1995b;Shiyanov et al, 1996). The competition for cyclin/cdk interactions may extend to kinase substrates which do not form stable interactions with cyclin/cdk complexes if this activity requires the same binding site occupied by p130, p107, p21 cip1 and p27 kip1 .…”

Section: Discussionmentioning

confidence: 99%

Identification of a p130 domain mediating interactions with cyclin A/cdk 2 and cyclin E/cdk 2 complexes

Lacy

Whyte

1997

Oncogene

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Section: Discussionmentioning

confidence: 99%

Identification of a p130 domain mediating interactions with cyclin A/cdk 2 and cyclin E/cdk 2 complexes

Lacy

Whyte

1997

Oncogene

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“…Cdk inhibition is not su cient for triggering granulocytic di erentiation p130 is known to bind cyclin E-Cdk2 or cyclin ACdk2 and, as a result, is capable of inhibiting Cdk2 activity at least in vitro (Zhu et al, 1995;Woo et al, 1997;Castano et al, 1998). This Cdk inhibitory activity requires N-terminal and spacer regions of p130 which are not conserved in pRB.…”

Section: E Ect Of Adenovirus E1a Oncoprotein On G-csf-induced Granulomentioning

confidence: 99%

“…Among the pRB family proteins, p107 and p130 are structurally closer to each other than to pRB and share unique properties allowing interaction with cyclins and Cdks Faha et al, 1992;Lees et al, 1992;Cobrinik et al, 1993;Zhu et al, 1995;Smith and Nevins, 1995). Through this interaction, p107 and p130 are capable of inhibiting the kinase activity of cyclin ± Cdk complexes (Zhu et al, 1995;Woo et al, 1997;Castano et al, 1998).…”

Section: Introductionmentioning

confidence: 99%

“…Through this interaction, p107 and p130 are capable of inhibiting the kinase activity of cyclin ± Cdk complexes (Zhu et al, 1995;Woo et al, 1997;Castano et al, 1998). In addition, p107 and p130 selectively bind E2F-4 and E2F-5 (Beijersbergen et al, 1994;Hijmans et al, 1995;Sardet et al, 1995;Vairo et al, 1995), whereas pRB preferentially binds E2F-1, E2F-2 and E2F-3 (Ikeda et al, 1996;Moberg et al, 1996).…”

Section: Introductionmentioning

confidence: 99%

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Granulocytic differentiation of myeloid progenitor cells by p130, the retinoblastoma tumor suppressor homologue

et al. 1999

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The retinoblastoma protein (pRB) and the related pocket proteins, p107 and p130, play crucial roles in mammalian cell cycle control. Recent studies indicate that these pocket proteins are also involved in cellular di erentiation processes. We demonstrate in this work that the pRB-related p130 selectively accumulates during the in vitro di erentiation of the myeloid progenitor cell, 32Dcl3, into granulocyte in response to granulocytecolony stimulating factor (G-CSF). This G-CSF-dependent granulocytic di erentiation is blocked by the adenovirus E1A oncoprotein, which binds to and inactivates the pRB family of pocket proteins including p130. Furthermore, enforced overexpression of p130 but not pRB inhibits the myeloid cell proliferation that is concomitantly associated with granulocytic di erentiation morphologically characterized by nuclear segmentation. However, simple G1-cell cycle arrest induced by cytokine deprivation or ectopic overexpression of the p27 cyclin-dependent kinase inhibitor, or inhibition of E2F activities by dominant negative DP-1 is not su cient to trigger granulocytic di erentiation. The di erentiationpromoting activity of p130 in myeloid cells requires both the pocket domain and the spacer domain. Our results indicate that the pRB-related p130 plays a critical role in myeloid cell di erentiation and suggest that coupling of cell cycle exit with the cellular di erentiation program may be speci®cally achieved by p130.

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“…p21 protein can regulate cell cycle progression by at least four distinct biochemical mechanisms: inactivating cyclin-CDK enzymes (Gu et ai., 1993;Harper et al, 1993;Xiong et al, 1993a), inhibiting PCNA-dependent DNA replication (Flores-Rozas et a]., 1994; Waga et al, 1994), preventing phosphorylation and activation of CDKs by CAK (Aprelikova et al, 1995), and disrupting E2F-pl07 and E2F-pI30 from association with cyclin A-CDK2 (Zhu et al, 1995;Shiyanov et al, 1996). Such diverse biochemical functions of p21 largely result from the ability of this small protein to associate with several cellular proteins to form various distinct complexes, including binary complexes with CDKs, cyclins or PCNA, ternary complexes with a CDK and a cyclin, and quaternary complexes with a CDK, a cyclin, and PCNA.…”

mentioning

confidence: 99%

Purification and crystallization of cyclin‐dependent kinase inhibitor p21

R.¹,

Nichols²,

Ke³

1996

Protein Science

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p21, a universal inhibitor of mammalian cyclin-dependent kinases (CDK), regulates cell cycle progression by forming various distinct protein complexes with cyclins, CDKs, and the proliferating cell nuclear antigen. We have overexpressed recombinant human p21 in E. coli and purified active p2 1 to near homogeneity on a large scale. Crystals of recombinant p21 have been grown in the space group P2, a = 157.4, b = 152.7, c = 90.6 A, and fl = 92.7'. The diffraction data of the recombinant p21 have been collected to 2.5 and 3.5 8, resolution for the native crystal and two heavy atom derivatives of mercury and iridium.Keywords: cell cycle; crystallization; cyclin dependent kinase inhibitor; X-ray diffractionThe primary control of eukaryotic cell cycle progression is provided by the sequential formation, activation, and subsequent inactivation of a family of serinekhreonine protein kinases, consisting of a catalytic subunit, a CDK (cyclin-dependent kinase), and an activating regulatory subunit, a cyclin. The enzymatic activity of a CDK is regulated by at least three different mechanisms: cyclin binding and activation, subunit phosphorylation, and association with and inhibition by a CDK inhibitor (reviewed by Sherr and Roberts, 1995). In mammalian cells, there exist at least two distinct families of CDK inhibitors, represented by two prototype CDK inhibitors, p21 and p16. The p16 family currently includes four isolated genes (reviewed by Sherr and Roberts, 1995): p 1 61NK4" (also variously known as MTSI, CDK41, and CDKN2), pl5INK4' (also known as MTS2, PI^'^''^'), and ~1 9 '~~~~ (reviewed by Sherr and Roberts, 1995). p16 family inhibitors regulate two closely related CDKs (CDK4 and CDK6) through two distinct mechanisms: 1) formation of binary complexes with the catalytic CDK4 or CDK6 to prevent activation by cyclin D binding and

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p107 uses a p21CIP1-related domain to bind cyclin/cdk2 and regulate interactions with E2F.

Cited by 249 publications

References 44 publications

Identification of a p130 domain mediating interactions with cyclin A/cdk 2 and cyclin E/cdk 2 complexes

Identification of a p130 domain mediating interactions with cyclin A/cdk 2 and cyclin E/cdk 2 complexes

Granulocytic differentiation of myeloid progenitor cells by p130, the retinoblastoma tumor suppressor homologue

Purification and crystallization of cyclin‐dependent kinase inhibitor p21

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