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

Mori, Akio; Higashi, Hideaki; Hoshikawa, Yutaka; Imamura, Masahiro; Asaka, Masahiro; Hatakeyama, Masanori

doi:10.1038/sj.onc.1203044

Cited by 14 publications

(13 citation statements)

References 79 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This ®nding supports redundancy of cdki's for the p21 role in di erentiation. Indeed, p19 (Adachi et al, 1997), p27 (Matsumura et al, 1997) and Rb-family member p130 (shown to be capable of substituting for cdki's in knockout mice (Coats et al, 1999;Mori et al, 1999)) can initiate myeloid or megakaryocytic di erentiation upon transfection into cell lines.…”

Section: Involvement Of P21 In Differentiationmentioning

confidence: 99%

Cell cycle regulators and hematopoiesis

Steinman

2002

Oncogene

View full text Add to dashboard Cite

Section: Involvement Of P21 In Differentiationmentioning

confidence: 99%

Cell cycle regulators and hematopoiesis

Steinman

2002

Oncogene

View full text Add to dashboard Cite

“…Cells were cultured in RPMI 1640 medium containing 10% fetal calf serum and 20% WEHI-3B-conditioned medium (20% WEHI) as a source of interleukin 3 (IL-3). Stable transfectants that conditionally express p107HA, p107⌬S/T-P-HA, or E1A were created by transfecting pOPTET-BSD-p107HA, pOPTET-BSD-p107⌬S/ T-P-HA, or pOPTET-BSD-E1A into 6-1 cells by electroporation as described (34,38). Expression of the cDNA-directed proteins in these transfectants was repressed in medium containing 1 g/ml tetracycline (Tc) and was induced in medium containing 5 mM isopropyl ␤-D-thiogalactopyranoside (IPTG) for 24 h in the absence of Tc.…”

Section: Methodsmentioning

confidence: 99%

“…We have previously shown that growth of hematopoietic cells such as BaF3 and 32D is strongly inhibited by ectopic expression of p130, but not by pRB, even in its phosphorylationresistant form (34,38). In these cells, p130 prevents S phase entry, at least in part, through inhibiting the transcriptional activity of E2F-4 (34).…”

Section: P107-mediated S Phase Cell Cycle Inhibitionmentioning

confidence: 99%

“…We have previously shown that in certain hematopoietic cells, including BaF3 and 32D cells, ectopically expressed p130 inhibits the cell cycle in G 1 , whereas pRB, even in its phosphorylation-resistant form, fails to do so (34,38). Given this obser-vation, we wished to know the role of p107, which is structurally closer to p130 than pRB (4), in hematopoietic cell cycle regulation.…”

mentioning

confidence: 99%

See 1 more Smart Citation

Involvement of pRB-related p107 Protein in the Inhibition of S Phase Progression in Response to Genotoxic Stress

Kondo

Higashi

Nishizawa

et al. 2001

Journal of Biological Chemistry

Self Cite

View full text Add to dashboard Cite

pRB family pocket proteins consisting of pRB, p107, and p130 are thought to act as a set of growth regulators that inhibit the cell cycle transition from G 1 to S phases by virtue of their interaction with E2F transcription factors. When cells are committed to progressing through the cell cycle at the late G 1 restriction point, they are hyperphosphorylated by G 1 cyclin-cyclin-dependent kinase and are functionally inactivated. Consistent with such a G 1 regulatory role, pRB and p130 are abundantly expressed in quiescent cells. In contrast, p107 is present at low levels in the hypophosphorylated form in quiescent cells. As cells progress toward late G 1 to S phases, the levels of p107 increase, and the majority become hyperphosphorylated, suggesting a possible role of p107 in post-G 1 cell cycle regulation. In this study, we have demonstrated that a nonphosphorylatable and thus constitutively active p107 has the potential to inhibit S phase progression. The levels of the phosphorylation-resistant p107 required for the S phase inhibition are significantly less than those of endogenous p107. We further show herein that the exposure of cells to the DNA-damaging agent, cisplatin, provokes S phase arrest, which is concomitantly associated with the accumulation of hypophosphorylated p107. Furthermore, the S phase inhibitory response to cisplatin is augmented by the ectopic expression of wild type p107, although it is diminished by the adenovirus E1A oncoprotein, which counteracts the pocket protein functions. Because p107 is a major pRB family protein expressed in S phase cells, our results indicate that p107 participates in an inhibition of cell cycle progression in response to DNA damage in S phase cells.

show abstract

“…These substrates might be one or more positive regulators of granulocytic differentiation 45,46 and/or negative regulators of proliferation during granulocytic differentiation, including the p130 pocket protein, p27, STAT-3, and C/EBP␣. [47][48][49][50][51][52][53] To begin to test this hypothesis, we measured the expression of p130 before and after CUL-4A-HA2 and control cells were induced to differentiate into granulocytes. The expression of c-myc, whose expression must be downregulated for the differentiation of myeloid cell lineages, including granulocytes, was also measured in these cells.…”

mentioning

confidence: 99%

Enforced expression of CUL-4A interferes with granulocytic differentiation and exit from the cell cycle

Yang

Clapp

et al. 2003

Blood

View full text Add to dashboard Cite

The cullin family of proteins is involved in the ubiquitin-mediated degradation of cell cycle regulators. Relatively little is known about the function of the CUL-4A cullin, but its overexpression in breast cancer suggests CUL-4A might also regulate the cell cycle. In addition, since other cullins are required for normal development, we hypothesized that CUL-4A is involved in regulating cell cycle progression during differentiation. We observed that CUL-4A mRNA and protein levels decline 2.5-fold during the differentiation of PLB-985 myeloid cells into granulocytes. To examine the significance of this observation, we overexpressed CUL-4A in these cells and found that modest (< 2-fold), enforced expression of CUL-4A attenuates terminal granulocytic differentiation and instead promotes proliferation. This overexpression similarly affects the differentiation of these cells into macrophages. We recently reported that nearly one half of CUL-4A ؉/؊ mice are nonviable, and in this report, we show that the viable heterozygous mice, which have reduced CUL-4A expression, have dramatically fewer erythroid and multipotential progenitors than normal controls. Together these results indicate that appropriate CUL-4A expression is essential for embryonic development and for cell cycle regulation during IntroductionUbiquitin-mediated degradation plays a critical role in controlling the turnover of cell cycle regulators. 1,2 The adenosine triphosphate (ATP)-dependent attachment of ubiquitin to a ubiquitin-activating enzyme (E1) activates ubiquitin for transfer to a ubiquitinconjugating enzyme (E2) and then to a ubiquitin ligase (E3), which transfers ubiquitin to a substrate protein. 3 Repetition of this ubiquitin transferase reaction results in the attachment of a polyubiquitin chain to the substrate, which is then recognized by the 26S proteasome and degraded. Much of the ubiquitin pathway's substrate specificity derives from E3 ligases, so regulating E3 activity is a likely mechanism for controlling ubiquitin-mediated degradation. Cullins are a core component of a subset of E3 ligases (described below). In this report, we examine the function of the CUL-4A cullin and find it plays a role in regulating granulocytic differentiation.Multisubunit RING (Really Interesting New Gene) E3 ligases contain at least 5 subunits: a RING finger protein, an E2, an adaptor protein, a substrate recognition subunit, and a cullin. 3 An extensively studied type of multisubunit RING E3 is SCF (Skp1, Cdc53/cullin, F-box protein), which was initially characterized in Saccharomyces cerevisiae. 1,2 Skp1 (the adaptor protein), Cdc53(the cullin), and Rbx1 (the RING finger protein) make up the SCF core. This core binds an E2 and various F-box proteins (such as Cdc4, Grr1, and Met30), which are responsible for substrate recognition. The resulting SCF complexes (SCF Cdc4 , SCF Grr1 , and SCF Met30 ) target for degradation a variety of cell cycle regulators, including Sic1, Far1, Cdc6, Cln1, Cln2, Gic2, and Swe1.Mammals encode 6 cullins, Cul-1, Cul-2, Cul-3...

show abstract

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

Cited by 14 publications

References 79 publications

Cell cycle regulators and hematopoiesis

Cell cycle regulators and hematopoiesis

Involvement of pRB-related p107 Protein in the Inhibition of S Phase Progression in Response to Genotoxic Stress

Enforced expression of CUL-4A interferes with granulocytic differentiation and exit from the cell cycle

Contact Info

Product

Resources

About