# CELL CYCLE GENES AND CELLULAR SENESCENCE AND AGING

> **NIH NIH R01** · BAYLOR COLLEGE OF MEDICINE · 1993 · $156,892

## Abstract

Normal human cells in culture show a limited division potential known as
senescence.  Cells divide for a defined number of generations and then
fail to enter subsequent S phases.  Available evidence suggests that
senescent cells have intact a pathway that prevents some aspect of
activation of the cell cycle regulatory apparatus.  Our overall interests
are to determine what aspect of activation is absent, and whether
introduction of cell cycle regulatory genes and proteins that normally
promote entry into S phase can overcome this inactivation.  Recent
genetic and biochemical evidence suggests that the G1 to S phase
transition in the eukaryotic cell cycle is controlled, in part, by the
coordinate action of a protein kinase(s), p34cdc2, and its associated
regulatory subunits, cyclins.  The principal focus of this program will
be the analysis of the role that Cdk2 and Cdc2Hs protein kinases and G1
cyclins play in the process of senescence and the regulation of cell
cycle transitions.  Cdk2 is a Cdc2-related protein kinase that forms a
distinct sub-family of Cdc2 kinases.  It is currently believed that Cdk2,
which is found complexed with cyclin A, is involved in the control of DNA
replication and/or the G1-S transition.  Depletion of the Xenopus Cdk2
protein, but not the Cdc2 protein, blocks DNA replication in cycling
embryonic extracts in vitro.  Further evidence suggestive of an early
role in the cell cycle is that some CDK2 mRNA persists in G0 cells and,
when G0 cells are stimulated to enter the cell cycle, its mRNA levels
increase in G1 prior to the increase in CDC2Hs mRNAs.

The specific aims of this research are to use the G1 cyclins, CDK2 and
CDC2Hs genes as tools to:  1) explore the expression state of quiescent
and senescent cells with respect to key cell cycle regulators, 2)
determine the effects of removal of Cdk2 and other relevant proteins on
the progression of the cell cycle, 3) to explore regulation of Cdk2 by
phosphorylation, and 4) to determine if expression of combinations of
cyclins and p34 protein kinases can promote entry of quiescent or
senescent cells into S phase.  Our analysis of G1 control in senescent
cells is aimed at identifying those key regulators whose functions are
negatively regulated in aging cells.  This information can be used to
further elaborate the mechanisms by which negative regulation is
established in senescent cells.

## Key facts

- **NIH application ID:** 3123074
- **Project number:** 1R01AG011085-01
- **Recipient organization:** BAYLOR COLLEGE OF MEDICINE
- **SAM.gov UEI:** FXKMA43NTV21
- **Principal Investigator:** STEPHEN J ELLEDGE
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1993
- **Award amount:** $156,892
- **Award type:** 1
- **Project period:** 1993-01-01 → 1996-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3123074

## Citation

> US National Institutes of Health, RePORTER application 3123074, CELL CYCLE GENES AND CELLULAR SENESCENCE AND AGING (1R01AG011085-01). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3123074. Licensed CC0.

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